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11-05-2021
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免疫系は自己・非自己を識別し、微生物などの非自己を排除するだけでなく、広範な生命機能に関わり、生体の恒常性を保つのみならず、妊娠の成立などにも重要な役割を果たしている。しかし、過剰な免疫応答はアレルギーや自己免疫疾患を引き起こし、不十分な免疫応答は慢性感染症、発がんへとつながる。とりわけ、がんにおいては、免疫系は異常細胞を排除し発がんを抑制しているが（免疫監視）、がん細胞はやがて自身の免疫原性を低下させることなどに加えて、様々な免疫抑制機構を獲得することで免疫系から逃避し（免疫逃避）、臨床的な「がん」となる。当教室では、免疫系が保つ生体の恒常性と免疫異常によりもたらされる様々な病態を理解することでダイナミックな生命現象としての免疫系の本態にせまり、免疫監視から免疫逃避という免疫学の最も重要な課題の理解につなげる基礎からトランスレーショナル（橋渡し）研究までを進めている。

研究プロジェクト

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1. T細胞の多様性に着目した新規がん免疫療法に関する研究

がん環境下では様々な免疫細胞が機能し、がん細胞の排除あるいはがん細胞の生存維持に関わっている。とりわけ、がん細胞の排除に関わる免疫細胞としてCD8陽性T細胞（CD8+T cells）が存在する。CD8+T cellsはT細胞受容体（TCR）による抗原認識および副刺激により活性化し、がん細胞を選択的に攻撃することができる。一方で、がん環境は免疫チェックポイント分子・免疫抑制細胞・サイトカインの作用により免疫抑制状態を作り出し、その結果がん細胞はCD8+ T cellsの攻撃から逃れている。がんに対する免疫応答が減弱する理由としてこのようながんの逃避機構が考えられるが、がん局所に浸潤しているCD8+ T cellsの多様性が少ないことも要因である。CD8+ T cellsはそれぞれ一つの細胞につき一種類のTCRを発現し、TCRの種類によりCD8+ T cellsの多様性が決まる。TCRは抗原決定基（エピトープ）と呼ばれる抗原の一部を認識するため、CD8+ T cellsの多様性が高いほど抗原に反応できるCD8+ T cell数が増える。
我々は、このCD8＋ T cellsの多様性に着目した新たながん免疫療法の開発に向けた研究をおこなっている。研究アプローチとして、TCRの多様性が低い高齢マウスを用いた実験を試みている。T細胞は胸腺にて発達するため、胸腺でのTCRの分化に関わる分子に着目し、その分子を薬剤により制御することでTCRの多様性を回復させ、がん細胞を攻撃できるCD8+ T cellsを増加させる。その後、既存の免疫療法による治療をおこない、治療効果が向上するか否かを検討する。

2. 免疫チェックポイント阻害剤を利用した新規がん免疫療法の開発

Video gaming slots near me. 免疫チェックポイント分子はT細胞が活性化されると発現し、T細胞の機能を負に制御する。これにより、T細胞の過剰な活性化による自己免疫応答を抑えている。一方で、がん環境下においては免疫チェックポイント分子シグナルが入り易く、T細胞が抑制状態に維持されるため、がん細胞への免疫応答が原弱している。近年がん免疫治療薬として注目されている抗PD-1抗体は、免疫チェックポイント分子であるPD-1のシグナルを阻害する抗体医薬であり、これによってCD8+ T cellsの活性化が維持され、抗腫瘍免疫応答が増強される。抗PD-1抗体は難治性がん患者に対し劇的な効果を示しているが、その効果は限定的であるため、その効果を向上させる治療薬との併用治療法が期待されている。現在の臨床研究では標準治療として使用されている抗がん剤との併用療法が進められており、一定の延命効果が報告されている。我々は動物モデルを用い、新規併用治療法の候補となり得る薬剤の探索を進めている。中でも、新たながん治療薬として期待されているウイルス製剤との併用治療法の開発を進めている。

3. 免疫細胞に関連する転写因子の新たな制御機構の解明

生命活動を司る遺伝子の発現には様々な転写因子が働いている。免疫細胞においても同様であり、細胞の分化、機能、遊走等に関わる遺伝子発現も転写因子により制御されている。免疫抑制細胞として中心的役割を担う制御性T細胞（Tregs）において、その機能制御に重要な働きをしているFOXP3も転写因子であり、Tregsを見分ける分子マーカーとしても知られている。また、CD8+ T cellsの機能維持に重要な働きをする転写因子としてT-betおよびEomesが知られており、これらの発現差異により活性化の強さや生存性が制御されている。本研究ではこれらの細胞に存在する転写因子に着目し、がん局所あるいはT細胞の抗原への応答性の差異において、これらの転写因子の新たな制御機構の解明を目指している。本研究では、上記転写因子に対する抗体を用いた免疫沈降からタンパク質複合体を精製し、これらを質量分析にて解析し、新規タンパク質の同定を試みている。

4. がん患者検体を用いたがん免疫臨床研究 Live casino table games.

より良い免疫療法を開発するためには、がん患者体内の免疫応答を解析することが重要である。我々は各内科および外科教室と協力し、がん患者から血液またはがん組織を採取できる環境を整えている。患者体内において末梢血とがん局所のそれぞれに存在する免疫細胞の動態が異なるため、血液とがん組織の免疫細胞を比較することで、がん局所の免疫応答を増強できる新たな知見が得られると考えられる。また、抗CTLA-4抗体あるいは抗PD-1抗体を投与された患者由来の検体も入手しており、抗体治療前後での免疫応答の変化を解析することで、抗体治療に効果のある患者の選別や、自己免疫疾患発症の原因解明が可能になると考えている。さらに、腸内細菌あるいは口腔内細菌の解析も進めており、これらの細菌叢と免疫応答とのあらたな相関性を見出すことを目的としている。 Myvegas slots customer service.

5. 鈴木准教授のグループはCD8+CD122+細胞に関する免疫学研究を行っている。CD122はIL-2受容体β鎖で、マウスCD8+細胞中の10％くらいはCD122を元から発現している。そして、CD4+細胞のうちCD25すなわちIL-2受容体α鎖を発現している細胞が制御性T細胞である、これは坂口志文博士が見つけたが、なんとCD8+細胞中のCD122を発現している細胞も制御性T細胞であることを私（鈴木）が発表したのが2004年だからもう10年以上前になる。それよりさらに前の1995年、私はCD122のKOマウスを作り、そこから20年以上CD122やこのCD8+CD122+細胞に関わる研究をしてきた。
現在の研究テーマは、少しこの細胞の発見当初とは違ってきているが、以下の様な内容に分かれ、広がっている。
i) 制御性T細胞としてのCD8+CD122+細胞
　a) 細胞集団を絞り込んでより純粋な制御性細胞を得られるようにする。そのためのマーカーとしてCD49dが見つかったが、引き続きその他の候補もマイクロアレイ等を使って検索中である。できればCD4+Tregのfoxp3に相当するものをCD8+でも見つけたい。
　b）制御のメカニズムとしてはFas/FasL経路を使用した活性化T細胞の細胞死誘導が主体と考えられるが他のメカニズム（IL-10などのサイトカイン）も否定できない。
　c）ヒトのCD8+制御性T細胞
ヒトのCD8+ 細胞の様相はマウスとはかなり異なっている。まずCD8+細胞の他にCD8dim細胞が存在し、それらはTCR−CD122highであるのでNK細胞であるとわかる。そしてCD8+細胞の中にはCD122high の細胞はいない。そこで、マイクロアレイ法を駆使しCD8+CD122+細胞とCD8+CD122−細胞との比較で見つかってきた遺伝子がcxcr3であった。果たして、抗ヒトCXCR3抗体は、ヒト末梢血CD8+細胞の10〜20％を染め、マウスにおいてはCD8+CD122+細胞とほぼ同じ集団に限られて発現していた。以上のデータはCXCR３がヒトでマウスCD122の代わりに使えることを示すものと思われる。
d）骨髄移植後の免疫異常を予防もしくは抑制するT細胞
遺伝的背景が同一の個体間の移植(Syngeneic Transplantation) においては、通常免疫応答は起こらない（寛容状態になる）と考えられるが、実際はFasもしくはFasL を欠失したマウス（lprマウスやgldマウス）を使って骨髄移植を行うと酷い皮膚炎を起こしたり肺炎を起こして死亡したりする（我々の独自の実験結果。まだ論文発表されていない）。これは、移植片や宿主に対して免疫系が反応して起こったことではなく、外来性の抗原に対する免疫応答がうまく制御できていないためのように考えられる。このlprやgldマウスを用いた骨髄移植の実験系を発展させ、どの細胞が皮膚炎や肺炎の防止・抑制に働いているかを明らかにする（CD8+CD122+CD49dlow細胞である可能性はかなり高いと思われる。）。混合骨髄移植でgld yやlpr のパートナーとして、野生型マウスの他にCD8KOやCD4KO、その結果を見ながら目的の細胞を絞りこんでいくことが可能である。（目的の細胞はCD8+であると言うプレリミナリーな結果が出ている）。この最終的結果を示せば、骨髄移植後のGVHD（移植片対宿主病）と思われている免疫異常に対して、CD8+制御性T細胞の細胞療法を適応させることが現実味を帯びてくるのではないだろうか。
ii) メモリ細胞としてのCD8+CD122+細胞
いわゆるcentral memory T cellsは、このCD8+制御性T細胞とほぼ同じ細胞表面形質を持つ。CD8+CD122+CD62L+（マウス）CD8+CXCR3+CD45RO+CCR7+（ヒト）などと言われているが、両者は同一の細胞で、見方によって制御性細胞としての活性も示すし、メモリ細胞のようにも振る舞う（少なくともnaive細胞ではない）のかもしれない。いずれにせよ、CD8+CD122+CD49dlow細胞にメモリ細胞活性があるかどうかを早急に調べる。
iii) がん免疫への関わり
CDå8+CD122+CD49dlow細胞を臨床医学に応用しようとする場合、考えるべきことの第一にはどのような細胞を制御するかであるが、CD4+Tregは直接的にはCD4+細胞を制御することが主体と考えられ、CD8+制御性細胞の直接の「制御対象」でより大きな意味を持つものはCD8+T細胞と考えられる（CD4+細胞もCD8+制御性T細胞で制御されるが主にはCD4+Tregで制御される）。移植片の拒絶やがんに対する免疫応答は、最終的なエフェクターとしてCD8+細胞傷害性T細胞が重要となることが知られており、特に近年がんに対する免疫応答増強効果を狙った抗体薬の進歩が著しい。CD8+細胞傷害性T細胞を直接制御するCD8+制御性T細胞はがん免疫にとっても欠かせない重要なキャラクターである。

教員

構成員名役職所属
西川 博嘉教授分子細胞免疫学
赤塚 美樹特任教授分子細胞免疫学
石田 高司特任教授分子細胞免疫学
鈴木 治彦准教授分子細胞免疫学
日野原 邦彦特任准教授高等研究院/分子細胞免疫学
SEO Wooseok特任准教授分子細胞免疫学
伊藤 佐知子講師分子細胞免疫学
KOCHIN Vitaly特任助教分子細胞免疫学
杉山 大介助教分子細胞免疫学
加藤 真一郎特任助教分子細胞免疫学

研究実績

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  • 2020年
    1. The PD-1 expression balance between effector and regulatory T cell predicts the clinical efficacy of PD-1 blockade therapies. , Kumagai S, Togashi Y, Kamada T, Sugiyama E, Nishinakaumra H, Takeuchi Y, Kochin, V, Itahashi K, Maeda Y, Matsui S, Shibahara,T, Yamashita Y, Irie T, Tsuge A, Fukuoka S, Kawazoe A, Udagawa H, Kirita K, Aokage K, Ishii G, Kuwata T, Nakama K, Kawazu M, Ueno T, Yamazaki N, Goto K, Tsuboi M, Mano H, Doi T, Shitara K, Nishikawa H , Nat Immunol. （頁：Online ahead of print）, 2020年
    2. An oncogenic alteration creates a tumor microenvironment that promotes tumor progression by conferring a metabolic advantage to regulatory T cells. , Kumagai S, Togashi Y, Sakai C, Kawazoe A, Kawazu M, Ueno T, Sato E, Kuwata T, Kinoshita T, Yamamoto M, Nomura S, Tsukamoto T, Mano H, Shitara K, Nishikawa H , Immunity. , 53巻 1号 （頁：187-203.e8.） , 2020年
    3. Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer. , Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Sato E, Ishii G, Goto K, Shintani Y, Okumura M, Tsuboi M, Nishikawa H. , Sci Immunol. , 5巻 43号 （頁：pii: eaav3937） , 2020年
    4. The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma. , Nagasaki J, Togashi Y, Sugawara T, Itami M, Yamauchi N, Yuda J, Sugano M, Ohara Y, Minami Y, Nakamae H, Hino M, Takeuchi M, Nishikawa H , Blood Adv. , 4巻 17号 （頁：4069-4082） , 2020年
    5. Newly emerged immunogenic neoantigens in established tumors enable hosts to regain immunosurveillance in a T cell-dependent manner. , Muramatsu T, Noguchi T, Sugiyama D, Kanada Y, Fujimaki K, Ito S, Gotoh M, Nishikawa H , Int Immunol. , 2020年
    6. Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells. , Tanaka A*, Nishikawa H*, Noguchi S* (*equally contributed), Sugiyama D, Morikawa H, Takeuchi Y, Ha D, Shigeta N, Kitawaki T, Maeda Y, Saito T, Shinohara Y, Kameoka Y, Iwaisako K, Monma F, Ohishi K, Karbach J, Jäger E, Sawada K, Katayama N, Takahashi N, Sakaguchi S. , J Exp Med. , 217巻 2号 , 2020年
    7. The potential application of PD-1 blockade therapy for early-stage biliary tract cancer. , Umemoto K, Togashi Y, Arai Y, Nakamura H, Takahashi S, Tanegashima T, Kato M, Nishikawa T, Sugiyama D, Kojima M, Gotohda N, Kuwata T, Ikeda M, Shibata T, Nishikawa H , Int Immunol. , 32巻 4号 （頁：273-281） , 2020年
  • 2019年
    1. Tokunaga A, Sugiyama D, Maeda Y, Warner AB, Panageas KS, Ito S, Togashi Y, Sakai C, Wolchok JD, Nishikawa H: Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids. J Exp Med. Sep. 19, 2019
    2. Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, Sato E, Fukuoka S, Tada Y, Tanaka A, Morikawa H, Kawazoe A, Kinoshita T, Shitara K, Sakaguchi S, Nishikawa H.: PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci USA. 116 (20):9999-10008 2019
    3. Tanegashima T, Togashi Y, Azuma K, Kawahara A, Ideguchi K, Sugiyama D, Kinoshita F, Akiba J, Kashiwagi E, Takeuchi A, Irie T, Tatsugami K, Hoshino T, Eto M. Nishikawa H.: Immune suppression by PD-L2 against spontaneous and treatment-related antitumor immunity. Clin Cancer Res. 25(15):4808-4819 2019
    4. Togashi Y, Shitara K, Nishikawa H.: Regulatory T cells in cancer immunosuppression - Implications for anticancer therapy. Nat Rev Clin Oncol. 16(6):356-371 2019
    5. Ohue Y, Nishikawa H.: Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci. 110(7):2080-2089 2019
    6. Kochin V, Nishikawa H.: Meddling with meddlers: curbing regulatory T cells and augmenting antitumor immunity. Nagoya J Med Sci. 81(1):1-18 2019
    7. Datta M, Coussens LM, Nishikawa H, Hodi FS, Jain RK.: R Reprogramming the Tumor Microenvironment to Improve Immunotherapy: Emerging Strategies and Combination Therapies. Am Soc Clin Oncol Educ Book. Jan; 39:165-174 2019.
    8. Doi T, Muro K, Ishii H, Kato T, Tsushima T, Takenoyama M, Oizumi S, Gemmoto K, Suna H, Enokitani K, Kawakami T, Nishikawa H, Yamamoto N.: A phase 1 study of the anti-CC chemokine receptor 4 antibody, mogamulizumab, in combination with nivolumab in patients with advanced or metastatic solid tumors. Clin Cancer Res. Aug 27 2019.
    9. Ha D, Tanaka A, Kibayashi T, Tanemura A, Sugiyama D, Wing JB, Lim EL, Teng KWW, Adeegbe D, Newell EW, Katayama I, Nishikawa H, Sakaguchi S.: Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody. Proc Natl Acad Sci USA. 116(2):609-618 2019.
    10. Inozume T, Yaguchi T, Ariyasu R, Togashi Y, Ohnuma T, Honobe A, Nishikawa H, Kawakami Y, Kawamura T.: Analysis of the Tumor Reactivity of Tumor-Infiltrating Lymphocytes in a Metastatic Melanoma Lesion that Lost Major Histocompatibility Complex Class I Expression after Anti-PD-1 Therapy. J Invest Dermatol. 139(7):1490-1496. 2019.
    11. Kawazoe A, Shitara K, Kuboki Y, Bando H, Kojima T, Yoshino T, Ohtsu A, Ochiai A, Togashi Y, Nishikawa H, Doi T, Kuwata T.: Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer. 22(1):69-76 2019.
  • 2018年
    1. Tada Y, Togashi Y, Kotani D, Kuwata T, Sato E, Kawazoe A, Doi T, Wada H, Nishikawa H, Shitara K.: Targeting VEGFR2 with Ramucirumab strongly impacts effector/activated regulatory T cells and CD8+ T cells in the tumor microenvironment. J. ImmunoTher Cancer 6(1):106 2018
    2. Takeuchi Y, Tanemura A, Tada Y, Katayama I, Kumanogoh A, Nishikawa H.: Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma. Int Immunol. 30(1):13-22 2018
    3. Shitara K, Nishikawa H.: Regulatory T cells: a potential target in cancer immunotherapy. Ann NY Acad Sci. 1417 (1):104-115 2018
    4. Ueda T, Aokage K, Nishikawa H, Neri S, Nakamura H, Sugano M, Tane K, Miyoshi T, Kojima M, Fujii S, Kuwata T, Ochiai A, Kusumoto M, Suzuki K, Tsuboi M, Ishii G.: Clinical response to PD-1 blockade correlates with a sub-fraction ofripheral central memory CD4+ T cells in patients with malignant melanoma. J Cancer Res Clin Oncol. 44 (5):835-844 2018.
    5. Shitaoka K, Hamana H, Kishi H, Hayakawa Y, Kobayashi E, Sukegawa K, Piao X, Lyu F, Nagata T, Sugiyama D, Nishikawa H, Tanemura A, Katayama I, Murahashi M, Takamatsu Y, Tani K, Ozawa T, Muraguchi A.: Identification of Tumoricidal TCRs from Tumor-Infiltrating Lymphocytes by Single-Cell Analysis. Cancer Immunol Res. 6 (4):378-388 2018.
  • 2017年
    1. Togashi Y, Nishikawa H.: Suppression from beyond the grave. Nat Immunol. 18(12):1285-1286 2017
    2. Nishiwaki S, Sugiura I, Miyata Y, Saito S, Sawa M, Nishida T, Miyamura K, Kuwatsuka Y, Kohno A, Yuge M, Kasai M, Iida H, Kurahashi S, Osaki M, Goto T, Terakura S, Murata M, Nishikawa H and Kiyoi H.: Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study). Medicine Dec;96(52):e9568 2017.
    3. Enokida T, Nishikawa H.: Regulatory T cells, as a target in anticancer immunotherapy. Immunotherapy. 9(8):623-627 2017
    4. ogashi Y, Nishikawa H.: Regulatory T Cells: Molecular and Cellular Basis for Immunoregulation. Curr Top Microbiol Immunol. 2017 Sep 7.
    5. Doki N, Suyama M, Sasajima S, Ota J, Igarashi A, Mimura I, Morita H, Fujioka Y, Sugiyama D, Nishikawa H, Shimazu Y, Suda W, Takeshita K, Atarashi K, Hattori M, Sato E, Watakabe-Inamoto K, Yoshioka K, Najima Y, Kobayashi T, Kakihana K, Takahashi N, Sakamaki H, Honda K, Ohashi K.: Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation. Ann Hematol. 96 (9):1517-1523 2017.
    6. Nagase H, Takeoka T, Urakawa S, Morimoto-Okazawa A, Kawashima A, Iwahori K, Takiguchi S, Nishikawa H, Sato E, Sakaguchi S, Mori M, Doki Y and Wada H.: ICOS+ Foxp3+TILs in gastric cancer are prognostic markers and effector regulatory T cells associated with Helicobacter pylori. Int J Cancer. 140(3):686-695 2017.
    7. Takeoka T, Nagase H, Kurose K, Ohue Y, Yamasaki M, Takiguchi S, Sato E, Isobe M, Kanazawa T, Matsumoto M, Iwahori K, Kawashima A, Morimoto-Okazawa A, Nishikawa H, Oka M, Pan L, Venhaus R, Nakayama E, Mori M, Doki Y and Wada H.; NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC. J Immunother. Mar 23 2017.
    8. Hamano Y, Kida H, Ihara S, Murakami A, Yanagawa M, Ueda K, Honda O, Tripathi LP, Arai T, Hirose M, Hamasaki T, Yano Y, Kimura T, Kato Y, Takamatsu H, Otsuka T, Minami T, Hirata H, Inoue K, Nagatomo I, Takeda Y, Mori M, Nishikawa H, Mizuguchi K, Kijima T, Kitaichi M, Tomiyama N, Inoue Y and Kumanogoh A. Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody. Sci Rep. 7:43201. 2017.
  • 2016年
    1. Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, Atarashi K, Maeda Y, Hamaguchi M, Ohkura N, Sato E, Nagase H, Nishimura J, Yamamoto H, Takiguchi S, Tanoue T, Suda W, Morita H, Hattori M, Honda K, Mori M, Doki Y, Sakaguchi S. Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med, 22:679-684 2016
    2. Okubo K, Wada H, Tanaka A, Eguchi H, Hamaguchi M, Tomokuni A, Tomimaru Y, Asaoka T, Hama N, Kawamoto K, Kobayashi S, Marubashi S, Nagano H, Sakaguchi N, Nishikawa H, Doki Y, Mori M, Sakaguchi S.: Identification of Novel and Noninvasive Biomarkers of Acute Cellular Rejection After Liver Transplantation by Protein Microarray. Transplant Direct. 2(12):e118. eCollection 2016 Nov 18. 2016
    3. Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, Mimura I, Morita H, Sugiyama D, Nishikawa H, Hattori M, Hino Y, Ikegawa S, Yamamoto K, Toya T, Doki N, Koizumi K, Honda K, Ohashi K. Fecal microbiota transplantation for patients with steroid-resistant/dependent acute graft-versus-host disease of the gut. Blood, 2016.
    4. Haseda F, Imagawa A, Nishikawa H, Mitsui S, Tsutsumi C, Fujisawa R, Sano H, Murase-Mishiba Y, Terasaki J, Sakaguchi S, Hanafusa T.: Antibody to CMRF35-Like Molecule 2, CD300e A Novel Biomarker Detected in Patients with Fulminant Type 1 Diabetes. PLoS One. Aug 11;11(8):e0160576 2016.
    5. Ureshino H, Shindo T, Nishikawa H, Watanabe N, Watanabe E, Satoh N, Kitaura K, Kitamura H, Doi K, Nagase K, Kimura H, Samukawa M, Kusunoki S, Miyahara M, Shin-I T, Suzuki R, Sakaguchi S, Kimura S.: Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia. Cancer Immunol Res. 4(8):644-649 2016.
    6. Takeuchi Y, Nishikawa H.: Roles of regulatory T cells in cancer immunity. Int Immunol. Shimazu Y, Shimazu Y, Hishizawa M, Hamaguchi M, Nagai Y, Sugino N, Fujii S, Kawahara M, Kadowaki N, Nishikawa H, Sakaguchi S, Takaori-Kondo A.: Hypomethylation of the Treg-specific demethylated region in FOXP3 is a hallmark of the regulatory T-cell subtype in adult T-cell leukemia. Cancer Immunol Res. 4(2):136-145 2016.
    7. Shimazu Y, Shimazu Y, Hishizawa M, Hamaguchi M, Nagai Y, Sugino N, Fujii S, Kawahara M, Kadowaki N, Nishikawa H, Sakaguchi S, Takaori-Kondo A.: Hypomethylation of the Treg-specific demethylated region in FOXP3 is a hallmark of the regulatory T-cell subtype in adult T-cell leukemia. Cancer Immunol Res. 4(2):136-145 2016.
    8. Hayakawa Y, Kawada M, Nishikawa H, Ochiya T, Saya H, Seimiya H, Yao R, Hayashi M, Kai C, Matsuda A, Naoe T, Ohtsu A, Okazaki T, Saji H, Sata M, Sugimura H, Sugiyama Y, Toi M, Irimura T.: Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs. Cancer Sci. 107(2):189-202 2016.
    9. Akane K, Kojima S, Mak TW, Shiku H, Suzuki H. CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity. Proc Natl Acad Sci U S A, 113:2460-2465 2016
    10. Ito S, Tanaka Y, Oshino R, Okado S, Hori M, Isobe KI. GADD34 suppresses lipopolysaccharide-induced sepsis and tissue injury through the regulation of macrophage activation. Cell Death Dis, 7:e2219 2016
    11. Liu L, Ito S, Nishio N, Sun Y, Tanaka Y, Isobe K. GADD34 Promotes Tumor Growth by Inducing Myeloid-derived Suppressor Cells. Anticancer Res, 36:4623-4628 2016
    12. Tanaka Y, Ito S, Isobe K. Vancomycin-sensitive bacteria trigger development of colitis-associated colon cancer by attracting neutrophils. Sci Rep, 6:23920. 2016
    13. Hirohashi Y, Torigoe T, Tsukahara T, Kanaseki T, Kochin V, Sato N. Immune responses to human cancer stem-like cells/cancer-initiating cells. Cancer Sci, 107:12-17 2016
    14. Ito N, Kamiguchi K, Nakanishi K, Sokolovskya A, Hirohashi Y, Tamura Y, Murai A, Yamamoto E, Kanaseki T, Tsukahara T, Kochin V, Chiba S, Shimohama S, Sato N, Torigoe T. A novel nuclear DnaJ protein, DNAJC8, can suppress the formation of spinocerebellar ataxia 3 polyglutamine aggregation in a J-domain independent manner. Biochem Biophys Res Commun, 474:626-633. 2016
    15. Kajiwara T, Tanaka T, Kukita K, Kutomi G, Saito K, Okuya K, Takaya A, Kochin V, Kanaseki T, Tsukahara T, Hirohashi Y, Torigoe T, Hirata K, Sato N, Tamura Y. Hypoxia augments MHC class I antigen presentation via facilitation of ERO1-α-mediated oxidative folding in murine tumor cells. Eur J Immunol, 2016.
    16. Sasaki T, Kanaseki T, Shionoya Y, Tokita S, Miyamoto S, Saka E, Kochin V, Takasawa A, Hirohashi Y, Tamura Y, Miyazaki A, Torigoe T, Hiratsuka H, Sato N. Microenvironmental stresses induce HLA-E/Qa-1 surface expression and thereby reduce CD8(+) T-cell recognition of stressed cells. Eur J Immunol, 46:929-940. 2016
    17. Tanaka T, Kutomi G, Kajiwara T, Kukita K, Kochin V, Kanaseki T, Tsukahara T, Hirohashi Y, Torigoe T, Okamoto Y, Hirata K, Sato N, Tamura Y. Cancer-associated oxidoreductase ERO1-α drives the production of VEGF via oxidative protein folding and regulating the mRNA level. Br J Cancer, 114:1227-1234. 2016
  • 2015年
    1. Nishikawa H. Overview: New Modality for Cancer Treatment. Oncology, 2015;89 Suppl 1:33-35.
    2. Adeegbe DO, Nishikawa H. Regulatory T cells in cancer; can they be controlled? Immunotherapy, 2015;7:843-846.
    3. Miyara M, Chader D, Sage E, Sugiyama D, Nishikawa H, Bouvry D, Claër L, Hingorani R, Balderas R, Rohrer J, Warner N, Chapelier A, Valeyre D, Kannagi R, Sakaguchi S, Amoura Z, Gorochov G. Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3high regulatory T cells in humans. Proc Natl Acad Sci U S A, 2015;112:7225-7230.
    4. Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, Doi T, Suzuki S, Isobe M, Funakoshi T, Kakimi K, Nishikawa H, Udono H, Oka M, Ueda R, Nakayama E. Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients. Clin Cancer Res, 2015;21:4327-4336.
    5. Takada K, Van Laethem F, Xing Y, Akane K, Suzuki H, Murata S, Tanaka K, Jameson SC, Singer A, Takahama Y. TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells. Nat Immunol, 2015;16:1069-1076.
    6. Ito S, Tanaka Y, Oshino R, Aiba K, Thanasegaran S, Nishio N, Isobe K. GADD34 inhibits activation-induced apoptosis of macrophages through enhancement of autophagy. Sci Rep, 2015;5:8327.
    7. Tanaka Y, Ito S, Oshino R, Chen N, Nishio N, Isobe K. Effects of growth arrest and DNA damage-inducible protein 34 (GADD34) on inflammation-induced colon cancer in mice. Br J Cancer, 2015;113:669-679.
    8. Sun Y, Ito S, Nishio N, Tanaka Y, Chen N, Liu L, Isobe K. Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34. Oxid Med Cell Longev, 2015;2015:170309.
    9. Liu L, Ito S, Nishio N, Sun Y, Chen N, Tanaka Y, Isobe K. GADD34 Facilitates Cell Death Resulting from Proteasome Inhibition. Anticancer Res, 2015;35:5317-5324.
    10. Okabe M, Ito S, Nishio N, Tanaka Y, Isobe K. Thymic Epithelial Cells Induced from Pluripotent Stem Cells by a Three-Dimensional Spheroid Culture System Regenerates Functional T Cells in Nude Mice. Cell Reprogram, 2015;17:368-375.
    11. Thanasegaran S, Ito S, Nishio N, Uddin MN, Sun Y, Isobe K. Recruitment of Gr1(+)CD11b (+)F4/80 (+) population in the bone marrow and spleen by irradiation-induced pulmonary damage. Inflammation, 2015;38:465-475.
    12. Chen N, Nishio N, Ito S, Tanaka Y, Sun Y, Isobe K. Growth arrest and DNA damage-inducible protein (GADD34) enhanced liver inflammation and tumorigenesis in a diethylnitrosamine (DEN)-treated murine model. Cancer Immunol Immunother, 2015;64:777-789.
    13. Himeno T, Kamiya H, Naruse K, Cheng Z, Ito S, Shibata T, Kondo M, Kato J, Okawa T, Fujiya A, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K, Nakamura J. Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice. J Diabetes Res, 2015;2015:257230.
    14. Hirohashi Y, Torigoe T, Mariya T, Kochin V, Saito T, Sato N. HLA class I as a predictor of clinical prognosis and CTL infiltration as a predictor of chemosensitivity in ovarian cancer. Oncoimmunology, 2015;4:e1005507.
    15. Torvaldson E, Kochin V, Eriksson JE. Phosphorylation of lamins determine their structural properties and signaling functions. Nucleus, 2015;6:166-171.
  • 2014年
    1. Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I and Sakaguchi S; Detection of self-reactive CD8+　T cells with an anergic phenotype in healthy individuals. Science. 346(6216):1536-1540 2014
    2. Matsumoto M, Baba A, Yokota T, Nishikawa H, Ohkawa Y, Kayama H, Kallies A, Nutt SL, Sakaguchi S, Takeda K, Kurosaki T and Baba Y.; Interleukin-10-Producing Plasmablasts Exert Regulatory Function in Autoimmune Inflammation. Immunity. 41(6):1040-1051 2014
    3. Nishikawa H, Sakaguchi S; Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. Jan 9;27:1-7 2014.
    4. Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali DAA, Kappler JW, Matsuda S, Mimori T, Sakaguchi N and Shimon S.; Detection of T-cell responses to a ubiquitous cellular protein in autoimmune disease. Science. 346(6207):363-368 2014
    5. Saito T, Wada H, Yamasaki M, Miyata H, Nishikawa H, Sato E, Kageyama S, Shiku H, Mori M, Doki Y.; High expression of MAGE-A4 and MHC class I antigens in tumor cells and induction of MAGE-A4 immune responses are prognostic markers of CHP-MAGE-A4 cancer vaccine. Vaccine. 32(45):5901-5907 2014
    6. Wada H, Isobe M, Kakimi K, Mizote Y, Eikawa S, Sato E, Takigawa N, Kiura K, Tsuji K, Iwatsuki K, Yamasaki M, Miyata H, Matsushita H, Udono H, Seto Y, Yamada K, Nishikawa H, Pan L, Venhaus R, Oka M, Doki Y, Nakayama E.; Vaccination With NY-ESO-1 Overlapping Peptides Mixed With Picibanil OK-432 and Montanide ISA-51 in Patients With Cancers Expressing the NY-ESO-1 Antigen. J Immunother. Feb-Mar;37(2):84-92 2014.
    7. Morishima A, Hirano T, Nishikawa H, Nakai K, Sakaguchi S, Kumanogoh A.; Comprehensive exploration of autoantibody in Behçet's disease: A novel autoantibody to claudin-1, an essential protein for tight junctions, is identified. Joint Bone Spine. 2014 Apr 29. pii: S1297-319X(14)00083-9.
    8. Sun Y, Ito S, Nishio N, Tanaka Y, Chen N, Isobe K. Acrolein induced both pulmonary inflammation and the death of lung epithelial cells. Toxicol Lett, 2014;229:384-392.
    9. Nishio N, Ito S, Isobe K. Loss of GADD34 induces early age-dependent deviation to the myeloid lineage. Immunol Cell Biol, 2014;92:170-180.
    10. Liu L, Nishio N, Ito S, Tanaka Y, Isobe K. Negative regulation of GADD34 on myofibroblasts during cutaneous wound healing. Biomed Res Int, 2014;2014:137049.
    11. Isobe K, Cheng Z, Nishio N, Suganya T, Tanaka Y, Ito S. iPSCs, aging and age-related diseases. N Biotechnol, 2014;31:411-421.
    12. Ito T, Yamada S, Tanaka C, Ito S, Murai T, Kobayashi D, Fujii T, Nakayama G, Sugimoto H, Koike M, Nomoto S, Fujiwara M, Kodera Y. Overexpression of L1CAM is associated with tumor progression and prognosis via ERK signaling in gastric cancer. Ann Surg Oncol, 2014;21:560-568.
    13. Kochin V, Shimi T, Torvaldson E, Adam SA, Goldman A, Pack CG, Melo-Cardenas J, Imanishi SY, Goldman RD, Eriksson JE. Interphase phosphorylation of lamin A. J Cell Sci, 2014;127:2683-2696.
    14. de Thonel A, Hazoumé A, Kochin V, Isoniemi K, Jego G, Fourmaux E, Hammann A, Mjahed H, Filhol O, Micheau O, Rocchi P, Mezger V, Eriksson JE, Rangnekar VM, Garrido C. Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells. Cell Death Dis, 2014;5:e1016.
    15. Morita R, Nishizawa S, Torigoe T, Takahashi A, Tamura Y, Tsukahara T, Kanaseki T, Sokolovskaya A, Kochin V, Kondo T, Hashino S, Asaka M, Hara I, Hirohashi Y, Sato N. Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells. Cancer Sci, 2014;105:389-395.
    16. Tsukahara T, Emori M, Murata K, Hirano T, Muroi N, Kyono M, Toji S, Watanabe K, Torigoe T, Kochin V, Asanuma H, Matsumiya H, Yamashita K, Himi T, Ichimiya S, Wada T, Yamashita T, Hasegawa T, Sato N. Specific targeting of a naturally presented osteosarcoma antigen, papillomavirus binding factor peptide, using an artificial monoclonal antibody. J Biol Chem, 2014;289:22035-22047.
  • 2013年
    1. Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jäger E, Sakaguchi S. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci U S A, 2013;110:17945-17950.
    2. Atarashi K, Tanoue T, Suda W, Oshima K, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S Taniguchi T, Morita H, Hattori M and Honda K; Treg induction by a rationally selected Clostridia cocktail from the human microbiota. Nature. 500 (7461):232-236 2013
    3. Hirayama M*, Nishikawa H*, Nagata Y, Tsuji T, Kato T, Kageyama S, Ueda S, Sugiyama D, Hori S, Sakaguchi S, Ritter G, Old LJ, Gnjatic S, and Shiku H.; Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes. Eur J Immunol. 43 (4):989-1000 2013
    4. Adeegbe DO, Nishikawa H. Natural and induced T regulatory cells in cancer. Front Immunol, 2013;4:190.
    5. Noguchi T, Ritter G, Nishikawa H.; Antibody-based therapy in colorectal cancer. Immunotherapy. 5 (5):533-545 2013
    6. Muraoka D, Nishikawa H, Noguchi T, Wang L, Harada N, Sato E, Luescher I, Nakayama E, Kato T, Shiku H.; Establishment of animal models to analyze the kinetics and distribution of human tumor antigen-specific CD8+ T cells. Vaccine. 31(17):2110-2118 2013
    7. Gupta A, Nuber N, Esslinger C, Wittenbrink M, Treder M, Landshammer A, Noguchi T, Kelly M, Gnjatic S, Ritter E, von Boehmer L, Nishikawa H, Shiku H, Old LJ, Ritter G, Knuth A, and van den Broek M.; A novel human-derived monoclonal antibody against NY-ESO-1 improves the efficacy of chemotherapy. Cancer Immun. Jan;13:E3 2013.
    8. Fujiwara S, Wada H, Kawada J, Kawabata R, Takahashi T, Fujita J, Hirao T, Shibata K, Makari Y, Iijima S, Nishikawa H, Jungbluth A, Nakamura Y, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Nakayama E, Mori M, and Doki Y.; NY-ESO-1 antibody as a novel tumor marker of gastric cancer. Br J Cancer 108 (5):1119-1125 2013.
    9. Liu B, Ohishi K, Orito Y, Nakamori Y, Nishikawa H, Ino K, Suzuki K, Matsumoto T, Masuya M, Hamada H, Mineno J, Ono R, Nosaka T, Shiku H, Katayama N.; Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: Potential utility for adoptive immunotherapy. Exp Hematol. 41(4):367-376 2013.
    10. Eikawa S, Kakimi K, Isobe M, Kuzushima K, Luescher I, Ohue Y, Ikeuchi K, Uenaka A, Nishikawa H, Udono H, Oka M, Nakayama E.; Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide. Int J Cancer. 2013 132(2):345-354.
    11. Okuno Y, Murakoshi A, Negita M, Akane K, Kojima S, Suzuki H. CD8+ CD122+ regulatory T cells contain clonally expanded cells with identical CDR3 sequences of the T-cell receptor β-chain. Immunology, 2013;139:309-317.
    12. Shozib HB, Suzuki H, Iino S, Nakayama S. Acceleration of ileal pacemaker activity in mice lacking interleukin 10. Inflamm Bowel Dis, 2013;19:1577-1585.
    13. Ito S, Tanaka Y, Nishio N, Thanasegaran S, Isobe K. Establishment of self-renewable GM-CSF-dependent immature macrophages in vitro from murine bone marrow. PLoS One, 2013;8:e76943.
    14. Cheng Z, Ito S, Nishio N, Thanasegaran S, Fang H, Isobe K. Characteristics of cardiac aging in C57BL/6 mice. Exp Gerontol, 2013;48:341-348.
    15. Thanasegaran S, Cheng Z, Ito S, Nishio N, Isobe K. No immunogenicity of IPS cells in syngeneic host studied by in vivo injection and 3D scaffold experiments. Biomed Res Int, 2013;2013:378207.
    16. Himeno T, Kamiya H, Naruse K, Cheng Z, Ito S, Kondo M, Okawa T, Fujiya A, Kato J, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K, Nakamura J. Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem cells ameliorate diabetic polyneuropathy in mice. Biomed Res Int, 2013;2013:259187.
    17. Kito T, Shibata R, Ishii M, Suzuki H, Himeno T, Kataoka Y, Yamamura Y, Yamamoto T, Nishio N, Ito S, Numaguchi Y, Tanigawa T, Yamashita JK, Ouchi N, Honda H, Isobe K, Murohara T. iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis. Sci Rep, 2013;3:1418.
    18. Okawa T, Kamiya H, Himeno T, Kato J, Seino Y, Fujiya A, Kondo M, Tsunekawa S, Naruse K, Hamada Y, Ozaki N, Cheng Z, Kito T, Suzuki H, Ito S, Oiso Y, Nakamura J, Isobe K. Transplantation of neural crest-like cells derived from induced pluripotent stem cells improves diabetic polyneuropathy in mice. Cell Transplant, 2013;22:1767-1783.
    19. Emori M, Tsukahara T, Murase M, Kano M, Murata K, Takahashi A, Kubo T, Asanuma H, Yasuda K, Kochin V, Kaya M, Nagoya S, Nishio J, Iwasaki H, Sonoda T, Hasegawa T, Torigoe T, Wada T, Yamashita T, Sato N. High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma. PLoS One, 2013;8:e84187.
    20. Saijo H, Hirohashi Y, Torigoe T, Kochin V, Takahashi H, Sato N. Cytotoxic T lymphocytes: the future of cancer stem cell eradication? Immunotherapy, 2013;5:549-551.
    21. Takahashi A, Hirohashi Y, Torigoe T, Tamura Y, Tsukahara T, Kanaseki T, Kochin V, Saijo H, Kubo T, Nakatsugawa M, Asanuma H, Hasegawa T, Kondo T, Sato N. Ectopically expressed variant form of sperm mitochondria-associated cysteine-rich protein augments tumorigenicity of the stem cell population of lung adenocarcinoma cells. PLoS One, 2013;8:e69095.
    22. Yasuda K, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, Kochin V, Asanuma H, Hasegawa T, Saito T, Hirohashi Y, Sato N. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population. PLoS One, 2013;8:e68187.
  • 2012年
    1. Nishikawa H*, Maeda Y*, Ishida T*, Gnjatic S, Sato E, Mori F, Sugiyama D, Ito A, Fukumori Y, Utsunomiya A, Inagaki H, Old LJ, Ueda R and Sakaguchi S; Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. Blood. 119:3097-3104 2012
    2. Noguchi T, Kato T, Wang L, Maeda Y, Ikeda H, Sato E, Knuth A, Gnjatic S, Ritter G, Sakaguchi S, Old LJ, Shiku H, and Nishikawa H.; Intracellular tumor-associated antigens represent effective targets for passive immunotherapy. Cancer Res. 72:1672-1682 2012
    3. Nakamori Y, Liu B, Ohishi K, Suzuki K, Ino K, Matsumoto T, Masuya M, Nishikawa H, Shiku H, Hamada H, Katayama N; Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors: a principal role for flt3 ligand in lymphopoiesis. Br J Haematol. 157(6):674-686 2012
    4. Fujiwara S, Wada H, Miyata H, Kawada J, Kawabata R, Nishikawa H, Gnjatic S, Sedrak C, Sato E, Nakamura Y, Sakakibara M, Kanto T, Shimosegawa E, Hatazawa J, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Takiguchi S, Nakayama E, Mori M, Doki Y.; Clinical Trial of the Intratumoral Administration of Labeled DC Combined With Systemic Chemotherapy for Esophageal Cancer. J. Immunother. 35(6):513-521 2012.
    5. Suzuki S, Masaki A, Ishida T, Ito A, Mori F, Sato F, Narita T, Ri M, Kusumoto S, Komatsu H, Fukumori Y, Nishikawa H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R.; Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma. Cancer Sci. 103(10):1764-1773 2012.
    6. Iwami K, Shimato S, Ohno M, Okada H, Nakahara N, Sato Y, Yoshida J, Suzuki S, Nishikawa H, Shiku H, Natsume A, Wakabayashi T.; Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor α2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele. Cytotherapy. 14 (6):733-742 2012.
    7. Kawada J, Wada H, Isobe M, Gnjatic S, Nishikawa H, Jungbluth AA, Okazaki N, Uenaka A, Nakamura Y, Fujiwara S, Mizuno N, Saika T, Ritter E, Yamasaki M, Miyata M, Ritter G, Murphy R, Hoffman EW, Pan L, Old LJ, Doki Y, Nakayama E.; Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination. Int J Cancer. 130:584-592 2012.
    8. Ito S, Nishio N, Isobe K. Analysis of b-amyloid peptide-binding proteins in microglial cells. The Open geriatric medicine journal, 2012; 5: 1-6.
    9. Isobe K, Cheng Z, Ito S, Nishio N. Aging in the mouse and perspectives of rejuvenation through induced pluripotent stem cells (iPSCs). Results Probl Cell Differ, 2012;55:413-427.
    10. Suzuki H, Shibata R, Kito T, Yamamoto T, Ishii M, Nishio N, Ito S, Isobe K, Murohara T. Comparative angiogenic activities of induced pluripotent stem cells derived from young and old mice. PLoS One, 2012;7:e39562.
    11. Uddin MN, Nishio N, Ito S, Suzuki H, Isobe K. Autophagic activity in thymus and liver during aging. Age (Dordr), 2012;34:75-85.
    12. Hirohashi Y, Torigoe T, Inoda S, Morita R, Kochin V, Sato N. Cytotoxic T lymphocytes: Sniping cancer stem cells. Oncoimmunology, 2012;1:123-125.
    13. Mori T, Nishizawa S, Hirohashi Y, Torigoe T, Tamura Y, Takahashi A, Kochin V, Fujii R, Kondo T, Greene MI, Hara I, Sato N. Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population. Exp Mol Pathol, 2012;92:27-32.
  • 2011年
    1. Toda M, Wang L, Ogura S, Torii M, Kurachi M, Kakimi K, Nishikawa H, Matsushima K, Shiku H, Kuribayashi K, Kato T.; UV irradiation of immunized mice induces type 1 regulatory T cells that suppress tumor antigen specific CTL responses. Int J Cancer. 129:1126-1136 2011.
    2. Endharti AT, Okuno Y, Shi Z, Misawa N, Toyokuni S, Ito M, Isobe K, Suzuki H. CD8+CD122+ regulatory T cells (Tregs) and CD4+ Tregs cooperatively prevent and cure CD4+ cell-induced colitis. J Immunol, 2011;186:41-52.
    3. Hayakawa A, Suzuki H, Kamei Y, Tanuma S, Magae J. Cladribine enhances apoptotic cell death in lung carcinoma cells over-expressing DNase γ. Biol Pharm Bull, 2011;34:1001-1004.
    4. Cheng Z, Ito S, Nishio N, Xiao H, Zhang R, Suzuki H, Okawa Y, Murohara T, Isobe K. Establishment of induced pluripotent stem cells from aged mice using bone marrow-derived myeloid cells. J Mol Cell Biol, 2011;3:91-98.
    5. Zhang R, Ito S, Nishio N, Cheng Z, Suzuki H, Isobe KI. Dextran sulphate sodium increases splenic Gr1(+)CD11b(+) cells which accelerate recovery from colitis following intravenous transplantation. Clin Exp Immunol, 2011;164:417-427.
    6. Zhang R, Ito S, Nishio N, Cheng Z, Suzuki H, Isobe K. Up-regulation of Gr1+CD11b+ population in spleen of dextran sulfate sodium administered mice works to repair colitis. Inflamm Allergy Drug Targets, 2011;10:39-46.
    7. Uddin MN, Ito S, Nishio N, Suganya T, Isobe K. Gadd34 induces autophagy through the suppression of the mTOR pathway during starvation. Biochem Biophys Res Commun, 2011;407:692-698.
    8. Inami Y, Yoshikai T, Ito S, Nishio N, Suzuki H, Sakurai H, Isobe K. Differentiation of induced pluripotent stem cells to thymic epithelial cells by phenotype. Immunol Cell Biol, 2011;89:314-321.
  • 2010年
    1. Muraoka D, Kato T, Wang L, Maeda Y, Noguchi T, Harada N, Takeda K, Yagita H, Guillaume P, Luescher I, Old LJ, Shiku H and Nishikawa H.; Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells. J Immunol. 185:3768-3776 2010
    2. Mitsui J*, Nishikawa H*, Muraoka D, Wang L, Noguchi T, Sato E, Kondo S, Allison JP, Sakaguchi S, Old LJ, Kato T and Shiku H.; Two distinct mechanisms of augmented anti-tumor activity by modulation of immuno-stimulatory/ inhibitory signals. Clin Cancer Res. 6:2781-2791 2010
    3. Nishikawa H and Sakaguchi S.; Regulatory T cells in Tumor Immunity. Int J Cancer. 127:759-767 2010
    4. Gnjatic S, Cao Y, Reichelt U. Yekebas EF, Nölker C, Marx A, Erbersdobler A, Nishikawa H, Hildebrandt Y, Bartels K, Horn C, Stahl T, Gout I, Filonenko V, Ling K-L, Cerundolo V, Luetkens T, Ritter G, Friedrichs K, Leuwer R, Hegewisch-Becker S, Jakob R. Izbicki JR, Bokemeyer C, Old LJ, Atanackovic D.; NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer. Int J Cancer. 127:381-393 2010.
    5. Burckhart T, Thiel M, Nishikawa H, Wüest T, Müller D, Zippelius A, Ritter G, Old L, Shiku H, Renner C.; Tumor-specific crosslinking of GITR as costimulation for immunotherapy. J Immunother. 33:925-934 2010.
    6. Wakita D, Sumida K, Iwakura Y, Nishikawa H, Ohkuri T, Chamoto K, Kitamura H, Nishimura T.; Tumor-infiltrating IL-17-producing γδ cells support the progression of tumor by promoting angiogenesis. Eur J Immunol. 40:1927-1937 2010.
    7. Torii M, Wang L, Ma N, Saito K, Hori T, Sato-Ueshima M, Koyama Y, Nishikawa H, Katayama N, Mizoguchi A, Shiku H, Yodoi J, Kuribayashi K, Kato T.; Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation. Eur J Immunol. 40:787-796 2010.
    8. Wadle A, Mischo A, Strahl S, Nishikawa H, Held G, Neumann F, Wullner B, Fischer E, Kleber S, Karbach J, Jager E, Shiku H, Odunsi K, Shrikant PA, Knuth A, Cerundolo V, Renner C.; NY-ESO-1 ptotein glycosylated by yeast induces enhanced immune responses. Yeast. 11:919-931 2010.
    9. Tanaka C, Ito S, Nishio S, Kodera Y, Sakurai H, Suzuki H, Nakao A, Isobe K.GADD34 suppresses wound healing by upregulating expression of myosin IIA Transgenic research 2010 Aug;19(4):637-45.
    10. Nishio N, Ito S, Suzuki H, Okawa Y and Isobe K.Effect of Aging on Auto-Antibodies to Wounded Tissues. The Open Geriatric Medicine Journal. 2010; 3;17-24.
    11. Suzuki H, Shibata R, Kito T, Ishii M, Li P, Yoshikai T, Nishio N, Ito S, Numaguchi Y, Yamashita JK, Murohara T, Isobe K.Therapeutic angiogenesis by transplantation of induced pluripotent stem cell-derived Flk-1 positive cells.BMC Cell Biol. 2010 Sep 22;11:72.
    12. de Thonel A, Ferraris SE, Pallari HM, Imanishi SY, Kochin V, Hosokawa T, Hisanaga S, Sahlgren C, Eriksson JE. Protein kinase Czeta regulates Cdk5/p25 signaling during myogenesis. Mol Biol Cell, 2010;21:1423-1434.
  • 2009年
    1. Aoki M, Ueda S, Nishikawa H, Kitano S, Hirayama M, Ikeda H, Toyoda H, Tanaka K, Kanai M, Takabayashi A, Imai H, Shiraishi T, Sato E, Wada H, Nakayama E, Takei Y, Katayama N, Shiku H, Kageyama S.; Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432. Vaccine. 27:6854-61 2009.
    2. Tahara H, Sato M, Thurin M, Wang E, Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Wigginton JM, Ambs S, Akutsu Y, Chaussabel D, Doki Y, Eremin O, Fridman WH, Hirohashi Y, Imai K, Jacobson J, Jinushi M, Kanamoto A, Kashani-Sabet M, Kato K, Kawakami Y, Kirkwood JM, Kleen TO, Lehmann PV, Liotta L, Lotze MT, Maio M, Malyguine A, Masucci G, Matsubara H, Mayrand-Chung S, Nakamura K, Nishikawa H, Palucka AK, Petricoin EF, Pos Z, Ribas A, Rivoltini L, Sato N, Shiku H, Slingluff CA, Streicher H, Stroncek DF, Takeuchi H, Toyota M, Wada H, Wu X, Wulfkuhle J, Yaguchi T, Zeskind B, Zhao Y, Zocca MB, Marincola FM.; Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology. J Transl Med. 7:45 2009.
    3. Wakita D, Chamoto K, Ohkuri T, Narita Y, Ashino S, Sumida K, Nishikawa H, Shiku H, Togashi Y, Kitamura H, Nishimura T.; IFN--dependent type 1 immunity is crucial for immunosurveillance against squamous cell carcinoma in a novel mouse carcinogenesis model. Carcinogenesis. 8:1408-1415 2009.
    4. Imai N, Ikeda H, Tawara I, Wang L, Wang L, Nishikawa H, Kato T, Shiku H.; Glucocorticoid-induced tumor necrosis factor receptor stimulation enhances the multifunctionality of adoptively transferred tumor antigen-specific CD8+ T cells with tumor regression. Cancer Sci. 100:1317-1325 2009.
    5. Hiasa A, Nishikawa H, Hirayama M, Kitano S, Okamoto S, Chono H, Yu SS, Mineno J, Tanaka Y, Minato N, Kato I, Shiku H.; Rapid αβ TCR-mediated responses in γδ T cells transduced with cancer-specific TCR genes. Gene Ther. 16:620-628 2009.
    6. Isikawa H, Ito S, Nishio N, Yuzawa Y, Matsuo S, Isobe K.Injection of bleomycin in newborn mice induces autoimmune sialitis that is transferred by CD4 T cells.Immunol Cell Biol. 2009 May-Jun:87(4) 351-358
    7. Nishio N, Ito S, Suzuki H, Isobe K.Antibodies to wounded tissue enhance cutaneous wound healing. Immunology. 2009 Nov128 (3)369-380
    8. Kaunisto A, Kochin V, Asaoka T, Mikhailov A, Poukkula M, Meinander A, Eriksson JE. PKC-mediated phosphorylation regulates c-FLIP ubiquitylation and stability. Cell Death Differ, 2009;16:1215-1226.
  • 2008年
    1. Nishikawa H, Kato T, Hirayama M, Orito Y, Sato E, Harada N, Gnjatic S, Old LJ, Shiku H. Regulatory T cell-resistant CD8+ T cells induced by glucocorticoid-induced tumor necrosis factor receptor signaling. Cancer Res, 2008;68:5948-5954.
    2. Hiasa A, Hirayama M, Nishikawa H, Kitano S, Nukaya I, Yu SS, Mineno J, Kato I Shiku H.; Long-term phenotypic, functional and genetic stability of cancer-specific T cell receptor (TCR) αβ genes transduced to CD8+ T cells. Gene Ther. 15:695-699 2008.
    3. Nishikawa H, Tsuji T, Jäger E, Briones G, Ritter G, Old LJ, Galán JE, Shiku H, Gnjatic S. Induction of regulatory T cell-resistant helper CD4+ T cells by bacterial vector. Blood, 2008;111:1404-1412.
    4. Kimura K, Ito S, Nagino M, Isobe K.Inhibition of reactive oxygen species down-regulates protein synthesis in RAW 264.7.Biochem Biophys Res Commun. 2008, Jul 18;372(1):272-275.
    5. Sasaki S, Ishida Y, Nishio N, Ito S, Isobe K.Thymic involution correlates with severe ulcerative colitis induced by oral administration of dextran sulphate sodium in C57BL/6 mice but not in BALB/c mice. Inflammation 2008 Oct 31(5):319-328
  • 2007年
    1. Ito S, Kimura K, Haneda M, Ishida Y, Sawada M, Isobe K.Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the microglia by amyloid-beta stimulation via the PI3K/Akt pathway.Exp Gerontol. 2007, June;42(6):532-537.
    2. Ishida Y, Okawa Y, Ito S, Shirokawa T, Isobe K.Age-dependent changes in dopaminergic projections from the substantia nigra pars compacta to the neostriatum. Neurosci Lett. 2007, May;418(3):257-261.
  • 2006年
    1. Nishikawa H, Sato E, Briones G, Chen LM, Matsuo M, Nagata Y, Ritter G, Jager E, Nomura H, Kondo S, Tawara I, Kato T, Shiku H, Old LJ, Galan JE, Gnjatic S. In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines. J Clin Invest. 116:1946-1954 2006.
    2. Nishikawa H, Qian F, Tsuji T, Ritter G, Old LJ, Gnjatic S., Odunsi K; Influence of CD4+CD25+ regulatory T cells on low/high-avidity CD4+ T cells following peptide vaccination. J Immunol. 176: 6340-6346 2006.
    3. Gnjatic S, Nishikawa H, Jungbluth AA, Gure AO, Ritter G, Jager E, Knuth A, Chen YT, Old LJ. NY-ESO-1: Review of an immunogenic tumor antigen. Adv Cancer Res. 95: 1-30 2006.
    4. Ogawa S, Tawara I, Ueno S, Kimura M, Miyazaki K, Nishikawa H, Yamaguchi M, Kobayashi T, Shiku H.; De novo CD5-positive diffuse large B-cell lymphoma of the temporal bone presenting with an external auditory canal tumor. Intern Med. 45:733-737 2006.
    5. Ito S, Sawada M, Haneda M, Ishida Y, Isobe K.Amyloid-beta peptides induce several chemokine mRNA expressions in the primary microglia and Ra2 cell line via the PI3K/Akt and/or ERK pathway.Neurosci Res. 2006 Nov;56(3):294-299.
    6. Isobe K, Ito S, Haneda M, Ishida Y.Cellular and systemic defense system against age-promoting stimuli.Nagoya J Med Sci. 2006 Jan;68(1-2):9-18.
    7. Du Y, Hirose N, Ping J, Ishida Y, Kojima T, Arai Y, Inagaki H, GondoY, Sakaki Y, Haneda M, Ito S, Isobe K.Analysis of growth hormone receptor polymorphism in Japanese semisuper centenarians.Geriatr Gerontol Int. 2006 June; 6(2):82-86.
    8. Kochin V, Imanishi SY, Eriksson JE. Fast track to a phosphoprotein sketch - MALDI-TOF characterization of TLC-based tryptic phosphopeptide maps at femtomolar detection sensitivity. Proteomics, 2006;6:5676-5682.
  • 2005年
    1. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 102:18538-18543 2005.
    2. Nishikawa H, Jäger E, Ritter G, Old LJ, Gnjatic S. CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients. Blood, 2005;106:1008-1011.
    3. Nishikawa H, Kato T, Tawara I, Ikeda H, Kuribayashi K, Allen PM, Schreiber RD, Old LJ, Shiku H.; Interferon-γ controls the generation/activation of CD4+ CD25+ regulatory T cells in anti-tumor immune response. J Immunol. 175: 4433-4440 2005.
    4. Nishikawa H, Kato T, Tawara I, Takemitsu T, Saito K, Wang L, Ikarashi Y, Wakasugi H, Nakayama T, Taniguchi M, Kuribayashi K, Old LJ, Shiku H. Accelerated chemically induced tumor development mediated by CD4+CD25+ regulatory T cells in wild-type hosts. Proc Natl Acad Sci U S A, 2005;102:9253-9257.
    5. Nishikawa H, Kato T, Tawara I, Saito K, Ikeda H, Kuribayashi K, Allen PM, Schreiber RD, Sakaguchi S, Old LJ, Shiku H. Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells. J Exp Med, 2005;201:681-686.
    6. Ito S, Sawada M, Haneda M, Fujii S, Oh-Hashi K, Kiuchi K, Takahashi M, Isobe K.Amyloid-beta peptides induce cell proliferation and macrophage colony-stimulating factor expression via the PI3-kinase/Akt pathway in cultured Ra2 microglial cells. FEBS Lett. 2005 Mar 28;579(9):1995-2000.

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