Immune checkpoints in the tumor microenvironment

被引：169

作者：

Toor, Salman M. ^{[1
]}

Nair, Varun Sasidharan ^{[1
]}

Decock, Julie ^{[1
]}

Elkord, Eyad ^{[1
,2
]}

机构：

[1] Hamad Bin Khalifa Univ HBKU, Qatar Biomed Res Inst QBRI, Canc Res Ctr, Qatar Fdn QF, POB 34110, Doha, Qatar

[2] Univ Manchester, Inst Canc Sci, Manchester, Lancs, England

来源：

SEMINARS IN CANCER BIOLOGY | 2020年 / 65卷

关键词：

Immune checkpoints; Immune checkpoint inhibitors; Tumor microenvironment; REGULATORY T-CELLS; LYMPHOCYTE-ACTIVATION GENE-3; PD-1; BLOCKADE; PROGNOSTIC VALUE; COMBINED NIVOLUMAB; INHIBITORY RECEPTORS; PROGRAMMED DEATH-1; LAG-3; EXPRESSION; UP-REGULATION; CANCER;

D O I：

10.1016/j.semcancer.2019.06.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Interactions between immune checkpoints (ICs) and their ligands negatively regulate T cell activation pathways involved in physiological immune responses against specific antigens. ICs and their ligands are frequently up-regulated in the tumor microenvironment (TME) of various malignancies, and they represent significant barriers for induction of effective anti-tumor immune responses. Several IC inhibitors (ICIs) have been developed, with some currently in clinical trials and others have been approved for the treatment of different cancers. However, tumor cells are able to counteract the activity of ICIs and can commission additional inhibitory pathways via expression of other ICs/ligands within the TME. This review discusses the expression of various ICs/ligands in the TME and their impact on tumor immune evasion. Additionally, we discuss various regulatory mechanisms, including genetic and epigenetic, and other modulatory factors including hypoxia and the presence of immunosuppressive populations in the TME, which result in upregulation of ICs in various cancers. Moreover, we discuss the prognostic significance of ICs and their ligands, and the potential strategies to enhance treatment responses to ICIs. This review aims to advance our current knowledge on the role of ICs in the TME and the clinical benefits of targeting them.

引用

页码：1 / 12

页数：12

共 195 条

[1] Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1 Expression in Patients with Non-Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis [J].