PD-1 and cancer: molecular mechanisms and polymorphisms

Salmaninejad, Arash and Khoramshahi, Vahid and Azani, Alireza and Soltaninejad, Ehsan and Aslani, Saeed and Zamani, Mohammad Reza and Zal, Masoud and Nesaei, Abolfazl and Hosseini, Sayed Mostafa (2017) PD-1 and cancer: molecular mechanisms and polymorphisms. Immunogenetics. ISSN 0093-7711

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Official URL: http://doi.org/10.1007/s00251-017-1015-5


The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers. In particular, PD-1 over-expression influences tumor-specific T cell immunity in a cancer microenvironment. Blocking the PD-1/PD-1 ligand (PD-L1) pathway could potentially augment endogenous antitumor responses. Along these lines, the use of PD-1/PD-L1 inhibitors has been applied in clinical trials against diverse forms of cancer. It was believed that antibodies targeting PD-1/PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity by blocking inhibitory receptor-ligand interactions. However, in all cases, the host genetic status (as well as that of the tumor) is likely to have an impact on the expected outcomes. Various investigations have evaluated the association between PD-1 polymorphisms and the risk of various types of cancer. Frequently studied PD-1 polymorphisms, PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.9 (rs2227982), and PD-1 rs7421861, and their associations in the risk of susceptibility to different types of cancer are mentioned in this review, as are studies highlighting the significance of conducting genetic association studies in different ethnic populations.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Unnamed user with email eprints@gmu.ac.ir
Date Deposited: 13 Sep 2017 07:27
Last Modified: 13 Sep 2017 07:27
URI: http://eprints.gmu.ac.ir/id/eprint/221

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