PD-1 and cancer: molecular mechanisms and polymorphisms

Area of Science:

• Immunology
• Genetics
• Oncology

Background:

• Programmed cell death protein 1 (PD-1) is an immunoregulatory molecule expressed on T cells, crucial for maintaining peripheral tolerance and regulating immune responses.
• PD-1 overexpression in cancer can lead to immune evasion by suppressing tumor-specific T cell immunity within the tumor microenvironment.
• The PD-1/PD-1 ligand (PD-L1) pathway is a target for cancer immunotherapy, with inhibitors showing promise in clinical trials.

Purpose of the Study:

• To review the role of PD-1 in immune regulation and cancer.
• To explore the association between PD-1 gene polymorphisms and cancer risk.
• To emphasize the significance of genetic association studies across different ethnic populations.

Main Methods:

• Literature review of studies investigating PD-1 function in immunity and cancer.
• Analysis of research on PD-1/PD-L1 pathway inhibitors in cancer therapy.
• Compilation of data on PD-1 polymorphisms (PD-1.1, PD-1.3, PD-1.5, PD-1.9, rs7421861) and their association with cancer susceptibility.

Main Results:

• PD-1 plays a critical role in T cell regulation, B cell responses, and monocyte activity.
• Overexpression of PD-1 contributes to tumor immune evasion.
• Several PD-1 polymorphisms have been studied for their association with various cancer risks.

Conclusions:

• Blocking the PD-1/PD-L1 pathway is a viable strategy for augmenting antitumor immunity.
• Host and tumor genetic status, including PD-1 polymorphisms, likely impact therapeutic outcomes.
• Further genetic association studies in diverse ethnic groups are essential to understand cancer susceptibility and treatment response related to PD-1.