CD8⁺ cytotoxic T lymphocytes in cancer immunotherapy: A review

Dec 7, 2018Journal of cellular physiology

Killer T Cells in Cancer Immunotherapy: A Review

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Abstract

CD8 cytotoxic T lymphocytes may face dysfunction and exhaustion in the tumor microenvironment due to various immunologic barriers.

Cancer-associated fibroblasts, M2 macrophages, and regulatory T cells can hinder the effectiveness of CD8 T cell-mediated antitumor responses.
Effector CD8 T cells infiltrate the tumor's core and are essential for targeting and killing cancer cells.
The process of CD8 T cell priming involves collaboration between innate immune cells and CD4 T cells.
Immunotherapy strategies, such as immune checkpoint blockade, may enhance CD8 T cell activity by increasing costimulatory signals.
Targeting PD-1 and CTLA-4 can help relieve CD8 T cell exhaustion and renew their priming against cancer.

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CD8cytotoxic T lymphocytes (CTLs) are preferred immune cells for targeting cancer. During cancer progression, CTLs encounter dysfunction and exhaustion due to immunerelated tolerance and immunosuppression within the tumor microenvironment (TME), with all favor adaptive immune-resistance. Cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and regulatory T cells (Tregs) could make immunologic barriers against CD8T cell-mediated antitumor immune responses. Thus, CD8T cells are needed to be primed and activated toward effector CTLs in a process called tumor immunity cycle for making durable and efficient antitumor immune responses. The CD8T cell priming is directed essentially as a corroboration work between cells of innate immunity including dendritic cells (DCs) and natural killer (NK) cells with CD4T cells in adoptive immunity. Upon activation, effector CTLs infiltrate to the core or invading site of the tumor (so-called infiltrated-inflamed [I-I] TME) and take essential roles for killing cancer cells. Exogenous reactivation and/or priming of CD8T cells can be possible using rational immunotherapy strategies. The increase of the ratio for costimulatory to coinhibitory mediators using immune checkpoint blockade (ICB) approach. Programmed death-1 receptor (PD-1)-ligand (PD-L1) and CTL-associated antigen 4 (CTLA-4) are checkpoint receptors that can be targeted for relieving exhaustion of CD8T cells and renewing their priming, respectively, and thereby eliminating antigen-expressing cancer cells. Due to a diverse relation between CTLs with Tregs, the Treg activity could be dampened for increasing the number and rescuing the functional potential of CTLs to induce immunosensitivity of cancer cells. + + + + + + +

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CD8⁺ cytotoxic T lymphocytes in cancer immunotherapy: A review

Abstract

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