Non-conventional Inhibitory CD4+Foxp3-PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity

被引：119

作者：

Zappasodi, Roberta ^{[1
,2
,3
]}

Budhu, Sadna ^{[1
,2
]}

Hellmann, Matthew D. ^{[3
,4
,5
]}

Postow, Michael A. ^{[4
,5
]}

Senbabaoglu, Yasin ^{[1
,2
]}

Manne, Sasikanth ^{[6
,7
]}

Gasmi, Billel ^{[1
,2
]}

Liu, Cailian ^{[1
,2
]}

Zhong, Hong ^{[1
,2
]}

Li, Yanyun ^{[1
,2
]}

Huang, Alexander C. ^{[3
,6
,7
]}

Hirschhorn-Cymerman, Daniel ^{[1
,2
]}

Panageas, Katherine S. ^{[8
]}

Wherry, E. John ^{[3
,6
,7
]}

Merghoub, Taha ^{[1
,2
,3
,4
]}

Wolchok, Jedd D. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Ludwig Collaborat, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Swim Amer Lab, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[5] Weill Cornell Med, New York, NY 10065 USA

[6] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[7] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA

[8] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10065 USA

来源：

CANCER CELL | 2018年 / 33卷 / 06期

关键词：

NIVOLUMAB PLUS IPILIMUMAB; GERMINAL CENTER FORMATION; FOLLICULAR HELPER-CELLS; MELANOMA MOUSE MODEL; B-CELLS; UNTREATED MELANOMA; LUNG-CANCER; OPEN-LABEL; IN-VIVO; CTLA-4;

D O I：

10.1016/j.ccell.2018.05.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A significant proportion of cancer patients do not respond to immune checkpoint blockade. To better understand the molecular mechanisms underlying these treatments, we explored the role of CD4(+)Foxp3(-) T cells expressing PD-1 (4PD1(hi)) and observed that 4PD1(hi) hi accumulate intratumorally as a function of tumor burden. Interestingly, CTLA-4 blockade promotes intratumoral and peripheral 4PD1(hi) increases in a dose-dependent manner, while combination with PD-1 blockade mitigates this effect and improves anti-tumor activity. We found that lack of effective 4PD1(hi) reduction after anti-PD-1 correlates with poor prognosis. Mechanistically, we provide evidence that mouse and human circulating and intra-tumor 4PD1(hi) inhibit T cell functions in a PD-1/PD-L1 dependent fashion and resemble follicular helper T cell (T-FH)-like cells. Accordingly, anti-CTLA-4 activity is improved in TFH deficient mice.

引用

页码：1017 / +

页数：23

共 63 条

[1] The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo [J].

Akiba, H ;

Takeda, K ;

Kojima, Y ;

Usui, Y ;

Harada, N ;

Yamazaki, T ;

Ma, J ;

Tezuka, K ;

Yagita, H ;

Okumura, K .

JOURNAL OF IMMUNOLOGY, 2005, 175 (04) :2340-2348

[2] An immunologic portrait of cancer [J].

Ascierto, Maria Libera ;

De Giorgi, Valeria ;

Liu, Qiuzhen ;

Bedognetti, Davide ;

Spivey, Tara L. ;

Murtas, Daniela ;

Uccellini, Lorenzo ;

Ayotte, Ben D. ;

Stroncek, David F. ;

Chouchane, Lotfi ;

Manjili, Masoud H. ;

Wang, Ena ;

Marincola, Francesco M. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2011, 9

[3] Combination of Alphavirus Replicon Particle-Based Vaccination with Immunomodulatory Antibodies: Therapeutic Activity in the B16 Melanoma Mouse Model and Immune Correlates [J].

Avogadri, Francesca ;

Zappasodi, Roberta ;

Yang, Arvin ;

Budhu, Sadna ;

Malandro, Nicole ;

Hirschhorn-Cymerman, Daniel ;

Tiwari, Shakuntala ;

Maughan, Maureen F. ;

Olmsted, Robert ;

Wolchok, Jedd D. ;

Merghoub, Taha .

CANCER IMMUNOLOGY RESEARCH, 2014, 2 (05) :448-458

[4] Interleukin-2 Inhibits Germinal Center Formation by Limiting T Follicular Helper Cell Differentiation [J].

Ballesteros-Tato, Andre ;

Leon, Beatriz ;

Graf, Beth A. ;

Moquin, Amy ;

Adams, Pamela Scott ;

Lund, Frances E. ;

Randall, Troy D. .

IMMUNITY, 2012, 36 (05) :847-856

[5] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[6] Persistent Antigen and Germinal Center B Cells Sustain T Follicular Helper Cell Responses and Phenotype [J].

Baumjohann, Dirk ;

Preite, Silvia ;

Reboldi, Andrea ;

Ronchi, Francesca ;

Ansel, K. Mark ;

Lanzavecchia, Antonio ;

Sallusto, Federica .

IMMUNITY, 2013, 38 (03) :596-605

[7] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[8] CD8+ T cell concentration determines their efficiency in killing cognate antigen expressing syngeneic mammalian cells in vitro and in mouse tissues [J].

Budhu, Sadna ;

Loike, John D. ;

Pandolfi, Ashley ;

Han, Soo ;

Catalano, Geoffrey ;

Constantinescu, Andrei ;

Clynes, Raphael ;

Silverstein, Samuel C. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (01) :223-235

[9] Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-γ levels in both nonmalignant and malignant prostate tissues [J].

Chen, Hong ;

Liakou, Chrysoula I. ;

Kamat, Ashish ;

Pettaway, Curtis ;

Ward, John F. ;

Tang, Derek Ng ;

Sun, Jingjing ;

Jungbluth, Achim A. ;

Troncoso, Patricia ;

Logothetis, Christopher ;

Sharma, Padmanee .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (08) :2729-2734

[10] LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor BcI6 [J].

Choi, Youn Soo ;

Gullicksrud, Jodi A. ;

Xing, Shaojun ;

Zeng, Zhouhao ;

Shan, Qiang ;

Li, Fengyin ;

Love, Paul E. ;

Peng, Weiqun ;

Xue, Hai-Hui ;

Crotty, Shane .

NATURE IMMUNOLOGY, 2015, 16 (09) :980-990

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