The tumor microenvironment shapes the molecular characteristics of exhausted CD8+ T cells

被引:33
作者
Cheng, Hongcheng [1 ,2 ,3 ]
Ma, Kaili [1 ,2 ]
Zhang, Lianjun [1 ,2 ]
Li, Guideng [1 ,2 ,3 ]
机构
[1] Suzhou Inst Syst Med, Suzhou 215123, Jiangsu, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Ctr Syst Med, Inst Basic Med Sci, Beijing 100005, Peoples R China
[3] Chinese Acad Med Sci, Key Lab Synthet Biol Regulatory Element, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
T cell exhaustion; Tumor microenvironment factors; Inhibitory receptors; Transcriptional factors; Immunotherapy; GROWTH-FACTOR; TRANSCRIPTION FACTOR; CHRONIC INFECTION; PD-1; EXPRESSION; IMMUNE-RESPONSE; LUNG-CANCER; EFFECTOR; BLOCKADE; CHECKPOINT; ANTITUMOR;
D O I
10.1016/j.canlet.2021.02.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The persistent antigen stimulation during chronic infections and cancer results in CD8(+) T cell exhaustion. The exhausted T (Tex) cells within the tumor microenvironment (TME) are characterized by increased expression of multiple co-inhibitory receptors simultaneously, progressive loss of effector function, poor proliferation and self-renewal capacity, and dysregulated metabolic activity. Emerging insights into molecular mechanisms underlying T cell exhaustion have proposed potential approaches to improve the efficacy of cancer immunotherapy via restoring the effector function of Tex cells. In this review, we summarize the fundamental characteristics (e.g., inhibitory receptors and transcriptional factors) regarding Tex cell differentiation and discuss in particular how those exhaustion features are acquired and shaped by key factors within the TME. Additionally, we discuss the progress and limitations of current cancer immunotherapeutic strategies targeting Tex cells in clinical setting.
引用
收藏
页码:55 / 66
页数:12
相关论文
共 163 条
[1]   Endogenous Glucocorticoid Signaling Regulates CD8+T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment [J].
Acharya, Nandini ;
Madi, Asaf ;
Zhang, Huiyuan ;
Klapholz, Max ;
Escobar, Giulia ;
Dulberg, Shai ;
Christian, Elena ;
Ferreira, Michelle ;
Dixon, Karen O. ;
Fell, Geoffrey ;
Tooley, Katherine ;
Mangani, Davide ;
Xia, Junrong ;
Singer, Meromit ;
Bosenberg, Marcus ;
Neuberg, Donna ;
Rozenblatt-Rosen, Orit ;
Regev, Aviv ;
Kuchroo, Vijay K. ;
Anderson, Ana C. .
IMMUNITY, 2020, 53 (03) :658-+
[2]   Transforming growth factor-β signaling: Tumorigenesis and targeting for cancer therapy [J].
Ahmadi, Amirhossein ;
Najafi, Masoud ;
Farhood, Bagher ;
Mortezaee, Keywan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (08) :12173-12187
[3]   TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection [J].
Alfei, Francesca ;
Kanev, Kristiyan ;
Hofmann, Maike ;
Wu, Ming ;
Ghoneim, Hazem E. ;
Roelli, Patrick ;
Utzschneider, Daniel T. ;
von Hoesslin, Madlaina ;
Cullen, Jolie G. ;
Fan, Yiping ;
Eisenberg, Vasyl ;
Wohlleber, Dirk ;
Steiger, Katja ;
Merkler, Doron ;
Delorenzi, Mauro ;
Knolle, Percy A. ;
Cohen, Cyrille J. ;
Thimme, Robert ;
Youngblood, Benjamin ;
Zehn, Dietmar .
NATURE, 2019, 571 (7764) :265-+
[4]   TOX provides a link between calcineurin activation and CD8 lineage commitment [J].
Aliahmad, P ;
O'Flaherty, E ;
Han, P ;
Goularte, OD ;
Wilkinson, B ;
Satake, M ;
Molkentin, JD ;
Kaye, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (08) :1089-1099
[5]   Development of all CD4 T lineages requires nuclear factor TOX [J].
Aliahmad, Parinaz ;
Kaye, Jonathan .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (01) :245-256
[6]   TOX Is Required for Development of the CD4 T Cell Lineage Gene Program [J].
Aliahmad, Parinaz ;
Kadavallore, Asha ;
de la Torre, Brian ;
Kappes, Dietmar ;
Kaye, Jonathan .
JOURNAL OF IMMUNOLOGY, 2011, 187 (11) :5931-5940
[7]   The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets [J].
Allard, Bertrand ;
Longhi, Maria Serena ;
Robson, Simon C. ;
Stagg, John .
IMMUNOLOGICAL REVIEWS, 2017, 276 (01) :121-144
[8]   Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies [J].
Anderson, Kristin G. ;
Stromnes, Ingunn M. ;
Greenberg, Philip D. .
CANCER CELL, 2017, 31 (03) :311-325
[9]   LAG3 (CD223) as a cancer immunotherapy target [J].
Andrews, Lawrence P. ;
Marciscano, Ariel E. ;
Drake, Charles G. ;
Vignali, Dario A. A. .
IMMUNOLOGICAL REVIEWS, 2017, 276 (01) :80-96
[10]   Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8+ T Cells [J].
Bachem, Annabel ;
Makhlouf, Christina ;
Binger, Katrina J. ;
de Souza, David P. ;
Tull, Deidra ;
Hochheiser, Katharina ;
Whitney, Paul G. ;
Fernandez-Ruiz, Daniel ;
Dahling, Sabrina ;
Kastemuller, Wolfgang ;
Jonsson, Johanna ;
Gressier, Elise ;
Lew, Andrew M. ;
Perdomo, Carolina ;
Kupz, Andreas ;
Figgett, William ;
Mackay, Fabienne ;
Oleshansky, Moshe ;
Russ, Brendan E. ;
Parish, Ian A. ;
Kallies, Axel ;
McConville, Malcolm J. ;
Tumer, Stephen J. ;
Gebhardt, Thomas ;
Bedoui, Sammy .
IMMUNITY, 2019, 51 (02) :285-+