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Title Alternative
Cancer immunotherapy with blocking of immune checkpoints
Author
Abstract
がんワクチンによる免疫治療では,如何にCD8T細胞を感作(プライミング)しその数を増やすか(免疫増強)という点に多大の努力が払われて来た.樹状細胞への抗原デリバリーと抗原プロセシング/提示,Toll様受容体などの刺激,即ち自然免疫系の活性化の併用などはそれに該当する.しかし十分に活性化されたT細胞をもってしても癌の拒絶は容易ではない.それには癌組織という特殊な環境が禍している.T細胞は癌塊内に入り込み莫大な数の癌細胞と遭遇する.癌組織内での繰り返す抗原認識の過程でT細胞は疲弊し,次第に本来あるべき機能を喪失していく.この疲弊(exhaustion)と呼ばれる現象は,T細胞に発現する複数の免疫抑制性分子―免疫チェックポイント分子―と腫瘍に発現するそのリガンドの結合によってもたらされる.代表的なチェックポイント分子の機能を抑制し,エフェクターT細胞が疲弊することなくその機能を長く維持できれば,これからのがん免疫治療に飛躍的な進展がみられるかもしれない.
Keywords
がんワクチン
CTL
免疫チェックポイント
T細胞疲弊
Note
総説(Review)
Published Date
2013-04-01
Publication Title
岡山医学会雑誌
Publication Title Alternative
Journal of Okayama Medical Association
Volume
volume125
Issue
issue1
Publisher
岡山医学会
Publisher Alternative
Okayama Medical Association
Start Page
13
End Page
18
ISSN
0030-1558
NCID
AN00032489
Content Type
Journal Article
Related Url
http://www.okayama-u.ac.jp/user/oma/
References
1) van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T : A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science (1991) 254, 1643-1647.
2) Rosenberg SA : Shedding light on immunotherapy for cancer. N Engl J Med (2004) 350, 1461-1463.
3) Rosenberg SA, Dudley ME, Restifo NP : Cancer immunotherapy. N Engl J Med (2008) 359, 1072.
4) Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW : Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science (1995) 270, 985-988.
5) Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH : Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity (1995) 3, 541-547.
6) Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, et al. : Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA (2003) 100, 8372-8377.
7) Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, Comin-Anduix B, Reuben JM, Seja E, Parker CA, Sharma A, Glaspy JA, et al. : Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675, 206. J Clin Oncol (2005) 23, 8968-8977.
8) Beck KE, Blansfield JA, Tran KQ, Feldman AL, Hughes MS, Royal RE, Kammula US, Topalian SL, Sherry RM, Kleiner D, Quezado M, Lowy I, et al. : Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol (2006) 24, 2283-2289.
9) Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, et al. : Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med (2010) 363, 711-723.
10) Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R : Restoring function in exhausted CD8 T cells during chronic viral infection. Nature (2006) 439, 682-687.
11) Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, et al. : Tumor-associated B7-H1 promotes T-cell apoptosis : a potential mechanism of immune evasion. Nat Med (2002) 8, 793-800.
12) Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF : PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8<sup>+</sup> T cells. Cancer Res (2004) 64, 1140-1145.
13) Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N : Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA (2002) 99, 12293-12297.
14) Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, et al. : Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors : safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol (2010) 28, 3167-3175.
15) Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK : The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol (2005) 6, 1245-1252.
16) Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ : Anti-TIM3 antibody promotes T cell IFN-&gamma;-mediated antitumor immunity and suppresses established tumors. Cancer Res (2011) 71, 3540-3551.
17) Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC : Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med (2010) 207, 2187-2194.
18) Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C, Kirkwood JM, Kuchroo V, Zarour HM : Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD<sup>+</sup> T cell dysfunction in melanoma patients. J Exp Med (2010) 207, 2175-2186.
19) Baitsch L, Legat A, Barba L, Fuertes Marraco SA, Rivals JP, Baumgaertner P, Christiansen-Jucht C, Bouzourene H, Rimoldi D, Pircher H, Rufer N, Matter M, et al. : Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization. PLoS One (2012) 7, e30852.
20) Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, Tangsombatvisit S, Grosso JF, et al. : Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res (2012) 72, 917-927.
21) Zarek PE, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, Drake CG, Powell JD : A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood (2008) 111, 251-259.
22) Martin F, Apetoh L, Ghiringhelli F : Controversies on
the role of Th17 in cancer : a TGF-&beta;-dependent immunosuppressive activity? Trends Mol Med (2012) 18, 742-749.
23) Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C, Wang E, Douek DC, et al. : A human memory T cell subset with stem cell-like properties. Nat Med (2011) 17, 1290-1297.
24) Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, Larsen CP, Ahmed R : mTOR regulates memory CD8 T-cell differentiation. Nature (2009) 460, 108-112.
25) Wang Y, Wang XY, Subjeck JR, Shrikant PA, Kim HL : Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. Br J Cancer (2011) 104, 643-652.
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日本語
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岡山大学
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Copyright (c) 2013 岡山医学会
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joma