Circulating PD-1⁺ effector memory T cells predict anti-PD-1 efficacy in advanced gastric cancer

Area of Science:

• Immunology
• Oncology
• Biomarker Discovery

Background:

• Gastric cancer (GC) treatment combines chemotherapy and immunotherapy (PD-1 blockade) with limited response rates.
• Predictive biomarkers are crucial for optimizing patient selection for chemo-immunotherapy.

Purpose of the Study:

• To identify a predictive biomarker for response to chemo-immunotherapy in advanced gastric cancer patients.
• To investigate the role of PD-1 expression on effector memory T cells (TEM) in predicting treatment outcomes.

Main Methods:

• Collected peripheral blood samples from 54 advanced GC patients treated with PD-1 inhibitors and platinum drugs.
• Assessed PD-1 expression on TEM cells and correlated it with treatment response (RECIST 1.1).
• Utilized univariate and multivariate analyses, alongside in vitro cytotoxicity and cytokine detection.

Main Results:

• A high pretreatment percentage of PD-1+ cells in TEM (cutoff 8.66%) was observed in responders versus non-responders (P=0.017).
• Higher PD-1+ TEM percentage independently predicted a protective factor for advanced GC patients receiving chemo-immunotherapy (HR=0.191, P=0.003).
• In vitro studies showed PD-1 blockade enhances TEM activation, increasing cytotoxicity and IFN-γ secretion.

Conclusions:

• A high pretreatment percentage of PD-1+ cells in TEM serves as a potential predictive biomarker for PD-1 blockade response in gastric cancer.
• This biomarker could aid in selecting patients likely to benefit from chemo-immunotherapy.