Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands

Kamali , A.N; Bautista , J.M; Eisenhut , M; Hamedifar, H

Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands

Authors

Kamali , A.N

Bautista , J.M

Eisenhut , M

Hamedifar, H

Issue Date

2023

Type

Scientific Paper

Keywords

Research Subject Categories::NATURAL SCIENCES::Biology::Cell and molecular biology::Immunology

Abstract

Abstract Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation. In the tumor microenvironment, T cells, as crucial immune response against malignant diseases as well as other immune central effector cells, such as natural killer cells, are regulated via co-stimulatory or co-inhibitory signals from immune or tumor cells. Studies have shown that exposure of T cells to tumor antigens upregulates the expression of inhibitory checkpoint receptors, leading to T-cell dysfunction or exhaustion. Although targeting immune checkpoint regulators has shown relative clinical efficacy in some tumor types, most trials in the field of cancer immunotherapies have revealed unsatisfactory results due to de novo or adaptive resistance in cancer patients. To overcome these obstacles, combinational therapies with newly discovered inhibitory molecules or combined blockage of several checkpoints provide a rationale for further research. Moreover, precise identification of their receptors counterparts at crucial checkpoints is likely to promise effective therapies. In this review, we examine the prospects for the application of newly emerging checkpoints, such as T-cell immunoglobulin and mucin domain 3, lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T-cell activation (VISTA), new B7 family proteins, and B- and T-cell lymphocyte attenuator, in association with immunotherapy of malignancies. In addition, their clinical and biological significance is discussed, including their expression in various human cancers, along with their roles in T-cell-mediated immune responses. Keywords: cancers; checkpoints inhibitors and immunotherapy; immune checkpoints. © The Author(s), 2023. PubMed Disclaimer Conflict of interest statement The authors declare that there is no conflict of interest. Figures Figure 1. Figure 1. A summarized overview of mechanisms… Similar articles Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy. Kamali AN, Hamedifar H, Eisenhut M, Bautista JM. Ther Adv Vaccines Immunother. 2024 Oct 9;12:25151355241288453. doi: 10.1177/25151355241288453. eCollection 2024. PMID: 39399301 Free PMC article. Review. Immune checkpoints and cancer development: Therapeutic implications and future directions. Mehdizadeh S, Bayatipoor H, Pashangzadeh S, Jafarpour R, Shojaei Z, Motallebnezhad M. 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Ther Adv Vaccines Immunother. 2024 Oct 9;12:25151355241288453. doi: 10.1177/25151355241288453. eCollection 2024. PMID: 39399301 Free PMC article. Review. Immune Checkpoints and Graves' Disease, Thyroid Eye Disease, and Orbital Myopathy: A Comprehensive Review. Souri Z, Pakdel F. J Ophthalmic Vis Res. 2024 Sep 16;19(3):368-380. doi: 10.18502/jovr.v19i3.15047. eCollection 2024 Jul-Sep. PMID: 39359534 Free PMC article. Review. Hyperoside Inhibits RNF8-mediated Nuclear Translocation of β-catenin to Repress PD-L1 Expression and Prostate Cancer. Chen J, Zhao Y, Wang X, Zang L, Yin D, Tan S. Anticancer Agents Med Chem. 2024;24(6):464-476. doi: 10.2174/0118715206289246240110044931. PMID: 38305391 References Pardoll D. Cancer and the immune system: basic concepts and targets for intervention. Semin Oncol 2015; 42: 523–538. - PMC - PubMed Castello A, Rossi S, Toschi L, et al.. Soluble PD-L1 in NSCLC patients treated with checkpoint inhibitors and its correlation with metabolic parameters. 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Citation

Kamali AN, Bautista JM, Eisenhut M, Hamedifar H. Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands. Ther Adv Vaccines Immunother. 2023 Aug 30;11:25151355231192043. doi: 10.1177/25151355231192043. PMID: 37662491; PMCID: PMC10469281.