T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment

被引:557
作者
Crespo, Joel [1 ,2 ,3 ]
Sun, Haoyu [4 ]
Welling, Theodore H. [1 ]
Tian, Zhigang [4 ]
Zou, Weiping [1 ,2 ,3 ]
机构
[1] Dept Surg, Ann Arbor, MI USA
[2] Grad Program Immunol & Tumor Biol, Ann Arbor, MI USA
[3] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[4] Univ Sci & Technol China, Inst Immunol, Sch Life Sci, Hefei 230026, Peoples R China
关键词
CHRONIC VIRAL-INFECTION; E3 UBIQUITIN LIGASE; GENE-TRANSCRIPTION; ANTITUMOR IMMUNITY; LYMPHOCYTE-T; REPLICATIVE SENESCENCE; INHIBITORY RECEPTORS; MOLECULAR SIGNATURE; MELANOMA PATIENTS; UP-REGULATION;
D O I
10.1016/j.coi.2012.12.003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human tumors progress despite the presence of tumor associated antigen (TAA)-specific T cells. Many different molecular and cellular mechanisms contribute to the failure of T cells to eradicate the tumor. These include immune suppressive networks that impair ongoing T cell function and enable tumor escape. Recent studies have started to reveal the nature of effector T cells in the tumor microenvironment. In this article we discuss T cell anergy, exhaustion, senescence, and sternness, and review the phenotype of dysfunctional T cell subsets and the underlying molecular mechanisms in the tumor microenvironments. We suggest that targeting T cell dysfunctional mechanisms and introducing/promoting T cell sternness are important approaches to treat patients with cancer.
引用
收藏
页码:214 / 221
页数:8
相关论文
共 76 条
[1]   LONG-TERM CULTURE OF MONOCLONAL HUMAN T-LYMPHOCYTES - MODELS FOR IMMUNOSENESCENCE [J].
ADIBZADEH, M ;
POHLA, H ;
REHBEIN, A ;
PAWELEC, G .
MECHANISMS OF AGEING AND DEVELOPMENT, 1995, 83 (03) :171-183
[2]   Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? [J].
Akbar, Arne N. ;
Henson, Sian M. .
NATURE REVIEWS IMMUNOLOGY, 2011, 11 (04) :289-295
[3]   GRAIL:: An E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells [J].
Anandasabapathy, N ;
Ford, GS ;
Bloom, D ;
Holness, C ;
Paragas, V ;
Seroogy, C ;
Skrenta, H ;
Hollenhorst, M ;
Fathman, CG ;
Soares, L .
IMMUNITY, 2003, 18 (04) :535-547
[4]   HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function [J].
Appay, V ;
Nixon, DF ;
Donahoe, SM ;
Gillespie, GMA ;
Dong, T ;
King, A ;
Ogg, GS ;
Spiegel, HML ;
Conlon, C ;
Spina, CA ;
Havlir, DV ;
Richman, DD ;
Waters, A ;
Easterbrook, P ;
McMichael, AJ ;
Rowland-Jones, SL .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :63-75
[5]   Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients [J].
Baitsch, Lukas ;
Baumgaertner, Petra ;
Devevre, Estelle ;
Raghav, Sunil K. ;
Legat, Amandine ;
Barba, Leticia ;
Wieckowski, Sebastien ;
Bouzourene, Hanifa ;
Deplancke, Bart ;
Romero, Pedro ;
Rufer, Nathalie ;
Speiser, Daniel E. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (06) :2350-2360
[6]   Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells [J].
Bandyopadhyay, Sanmay ;
Dure, Myrianne ;
Paroder, Monika ;
Soto-Nieves, Noemi ;
Puga, Irene ;
Macian, Fernando .
BLOOD, 2007, 109 (07) :2878-2886
[7]   Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[8]   Reversal of human cellular senescence:: roles of the p53 and p16 pathways [J].
Beauséjour, CM ;
Krtolica, A ;
Galimi, F ;
Narita, M ;
Lowe, SW ;
Yaswen, P ;
Campisi, J .
EMBO JOURNAL, 2003, 22 (16) :4212-4222
[9]   Coexpression of PD-1, 2B4, CD160 and KLRG1 on Exhausted HCV-Specific CD8+T Cells Is Linked to Antigen Recognition and T Cell Differentiation [J].
Bengsch, Bertram ;
Seigel, Bianca ;
Ruhl, Marianne ;
Timm, Joerg ;
Kuntz, Martin ;
Blum, Hubert E. ;
Pircher, Hanspeter ;
Thimme, Robert .
PLOS PATHOGENS, 2010, 6 (06)
[10]   Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection [J].
Blackburn, Shawn D. ;
Shin, Haina ;
Haining, W. Nicholas ;
Zou, Tao ;
Workman, Creg J. ;
Polley, Antonio ;
Betts, Michael R. ;
Freeman, Gordon J. ;
Vignali, Dario A. A. ;
Wherry, E. John .
NATURE IMMUNOLOGY, 2009, 10 (01) :29-37