Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

被引：344

作者：

Krishna, Sri ^{[1
]}

Lowery, Frank J. ^{[1
]}

Copeland, Amy R. ^{[1
]}

Bahadiroglu, Erol ^{[2
]}

Mukherjee, Ratnadeep ^{[2
]}

Jia, Li ^{[3
]}

Anibal, James T. ^{[2
]}

Sachs, Abraham ^{[1
]}

Adebola, Serifat O. ^{[2
]}

Gurusamy, Devikala ^{[1
]}

Yu, Zhiya ^{[1
]}

Hill, Victoria ^{[1
]}

Gartner, Jared J. ^{[1
]}

Li, Yong F. ^{[1
]}

Parkhurst, Maria ^{[1
]}

Paria, Biman ^{[1
]}

Kvistborg, Pia ^{[4
]}

Kelly, Michael C. ^{[5
]}

Goff, Stephanie L. ^{[1
]}

Altan-Bonnet, Gregoire ^{[2
]}

Robbins, Paul F. ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

机构：

[1] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NCI, Immunodynam Grp, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] Natl Inst Hlth Lib, NIH, Bethesda, MD 20892 USA

[4] Netherlands Canc Inst, Div Immunol, Amsterdam, Netherlands

[5] Frederick Natl Lab, Single Cell Anal Facil, Canc Res Technol Program, Bethesda, MD 20892 USA

来源：

SCIENCE | 2020年 / 370卷 / 6522期

关键词：

TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; TRANSFER THERAPY; MASS CYTOMETRY; BLOCKADE; PATIENT; IMMUNE; PERSISTENCE; SENSITIVITY; REGRESSION;

D O I：

10.1126/science.abb9847

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Adoptive T cell therapy (ACT) using ex vivo-expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39(-)CD69(-)) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39(+)CD69(+)) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39(+) state. However, ACT responders retained a pool of CD39(-) stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.

引用

页码：1328 / +

页数：51

共 62 条

[1] Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum
Bendall, Sean C.
Simonds, Erin F.
Qiu, Peng
Amir, El-ad D.
Krutzik, Peter O.
Finck, Rachel
Bruggner, Robert V.
Melamed, Rachel
Trejo, Angelica
Ornatsky, Olga I.
Balderas, Robert S.
Plevritis, Sylvia K.
Sachs, Karen
Pe'er, Dana
Tanner, Scott D.
Nolan, Garry P.
[J]. SCIENCE, 2011, 332 (6030) : 687 - 696
[2] Defining 'T cell exhaustion'
Blank, Christian U.
Haining, W. Nicholas
Held, Werner
Hogan, Patrick G.
Kallies, Axel
Lugli, Enrico
Lynn, Rachel C.
Philip, Mary
Rao, Anjana
Restifo, Nicholas P.
Schietinger, Andrea
Schumacher, Ton N.
Schwartzberg, Pamela L.
Sharpe, Arlene H.
Speiser, Daniel E.
Wherry, E. John
Youngblood, Benjamin A.
Zehn, Dietmar
[J]. NATURE REVIEWS IMMUNOLOGY, 2019, 19 (11) : 665 - 674
[3] Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, Andrew
Hoffman, Paul
Smibert, Peter
Papalexi, Efthymia
Satija, Rahul
[J]. NATURE BIOTECHNOLOGY, 2018, 36 (05) : 411 - +
[4] Elements of cancer immunity and the cancer-immune set point
Chen, Daniel S.
Mellman, Ira
[J]. NATURE, 2017, 541 (7637) : 321 - 330
[5] Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Chowell, Diego
Morris, Luc G. T.
Grigg, Claud M.
Weber, Jeffrey K.
Samstein, Robert M.
Makarov, Vladimir
Kuo, Fengshen
Kendall, Sviatoslav M.
Requena, David
Riaz, Nadeem
Greenbaum, Benjamin
Carroll, James
Garon, Edward
Hyman, David M.
Zehir, Ahmet
Solit, David
Berger, Michael
Zhou, Ruhong
Rizvi, Naiyer A.
Chan, Timothy A.
[J]. SCIENCE, 2018, 359 (6375) : 582 - +
[6] Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes
Cohen, Cyrille J.
Gartner, Jared J.
Horovitz-Fried, Miryam
Shamalov, Katerina
Trebska-McGowan, Kasia
Bliskovsky, Valery V.
Parkhurst, Maria R.
Ankri, Chen
Prickett, Todd. D.
Crystal, Jessica S.
Li, Yong F.
El-Gamil, Mona
Rosenberg, Steven A.
Robbins, Paul F.
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (10) : 3981 - 3991
[7] Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1c259 T Cells in Synovial Sarcoma
D'Angelo, Sandra P.
Melchiori, Luca
Merchant, Melinda S.
Bernstein, Donna
Glod, John
Kaplan, Rosandra
Grupp, Stephan
Tap, William D.
Chagin, Karen
Binder, Gwendolyn K.
Basu, Samik
Lowther, Daniel E.
Wang, Ruoxi
Bath, Natalie
Tipping, Alex
Betts, Gareth
Ramachandran, Indu
Navenot, Jean-Marc
Zhang, Hua
Wells, Daniel K.
Van Winkle, Erin
Kari, Gabor
Trivedi, Trupti
Holdich, Tom
Pandite, Lini
Amado, Rafael
Mackall, Crystal L.
[J]. CANCER DISCOVERY, 2018, 8 (08) : 944 - 957
[8] CD8+ Enriched "Young" Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma
Dudley, Mark E.
Gross, Colin A.
Langhan, Michelle M.
Garcia, Marcos R.
Sherry, Richard M.
Yang, James C.
Phan, Giao Q.
Kammula, Udai S.
Hughes, Marybeth S.
Citrin, Deborah E.
Restifo, Nicholas P.
Wunderlich, John R.
Prieto, Peter A.
Hong, Jenny J.
Langan, Russell C.
Zlott, Daniel A.
Morton, Kathleen E.
White, Donald E.
Laurencot, Carolyn M.
Rosenberg, Steven A.
[J]. CLINICAL CANCER RESEARCH, 2010, 16 (24) : 6122 - 6131
[9] Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients
Dudley, ME
Wunderlich, JR
Shelton, TE
Even, J
Rosenberg, SA
[J]. JOURNAL OF IMMUNOTHERAPY, 2003, 26 (04): : 332 - 342
[10] Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors
Duhen, Thomas
Duhen, Rebekka
Montler, Ryan
Moses, Jake
Moudgil, Tarsem
de Miranda, Noel F.
Goodall, Cheri P.
Blair, Tiffany C.
Fox, Bernard A.
McDermott, Jason E.
Chang, Shu-Ching
Grunkemeier, Gary
Leidner, Rom
Bell, Richard Bryan
Weinberg, Andrew D.
[J]. NATURE COMMUNICATIONS, 2018, 9

← 1 2 3 4 5 6 7 →