TY - JOUR
T1 - Immune checkpoint inhibitors in cancer therapy
T2 - A focus on T-regulatory cells: A
AU - Sasidharan Nair, Varun
AU - Elkord, Eyad
N1 - Publisher Copyright:
© 2017 Australasian Society for Immunology Inc.
PY - 2018/1
Y1 - 2018/1
N2 - Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME. Recent studies have shown that immune checkpoint molecules promote cancer progression through various antitumor inhibitory mechanisms. Recent advances in cancer immunotherapy have shown the promising potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune responses and clinical benefits in patients with cancer at late stages. Most studies revealed the effect of ICIs on T effector cells, and little is known about their effect on Tregs. In this review, we highlight the effects of the ICIs, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti-TIGIT, on tumor-infiltrating and peripheral Tregs to elicit effector T-cell functions against tumors. Additionally, we discuss how ICIs may target Tregs for cancer immunotherapy. Recent advances confirmed the key roles of the immune checkpoints in tumor progression, and their blockade showed promising potentials in cancer therapy. This review highlights the effect of immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti-TIGIT, on T regulatory cells to elicit potent anti-tumor immunities.
AB - Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME. Recent studies have shown that immune checkpoint molecules promote cancer progression through various antitumor inhibitory mechanisms. Recent advances in cancer immunotherapy have shown the promising potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune responses and clinical benefits in patients with cancer at late stages. Most studies revealed the effect of ICIs on T effector cells, and little is known about their effect on Tregs. In this review, we highlight the effects of the ICIs, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti-TIGIT, on tumor-infiltrating and peripheral Tregs to elicit effector T-cell functions against tumors. Additionally, we discuss how ICIs may target Tregs for cancer immunotherapy. Recent advances confirmed the key roles of the immune checkpoints in tumor progression, and their blockade showed promising potentials in cancer therapy. This review highlights the effect of immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti-TIGIT, on T regulatory cells to elicit potent anti-tumor immunities.
KW - cancer
KW - immune checkpoint inhibitors
KW - T-regulatory cells
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85034267218&partnerID=8YFLogxK
U2 - 10.1111/imcb.1003
DO - 10.1111/imcb.1003
M3 - Review article
C2 - 29359507
AN - SCOPUS:85034267218
SN - 0818-9641
VL - 96
SP - 21
EP - 33
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
IS - 1
ER -