Early Increase in Circulating PD-1(+)CD8(+) T Cells Predicts Favorable Survival in Patients with Advanced Gastric Cancer Receiving Chemotherapy

SIMPLE SUMMARY: There is a lack of biomarkers for predicting the response to chemotherapy in gastric cancer (GC). This study investigates the prognostic significance of PD-1 expression in CD8(+) T cells in the blood of 68 patients with advanced GC receiving platinum-based chemotherapy. Patients were divided based on baseline frequencies of PD-1(+)CD8(+) T cells and whether these frequencies increased or decreased on day 7 after treatment. While baseline frequencies of PD-1(+)CD8(+) T cells had no impact on survival, the patients whose frequencies of PD-1(+)CD8(+) T cells increased on day 7 from the treatment initiation showed significantly longer survival than those whose frequencies of PD-1(+)CD8(+) T cells decreased. This difference was also reflected in the mean duration of response between the groups. These findings suggest that an early increase in frequencies of PD-1(+)CD8(+) T cells could predict favorable prognoses and durable responses in patients with advanced GC receiving chemotherapy. ABSTRACT: The clinical significance of PD-1 expression in circulating CD8(+) T cells in patients with gastric cancer (GC) receiving chemotherapy remains unelucidated. Therefore, we aimed to examine its prognostic significance in blood samples of 68 patients with advanced GC who received platinum-based chemotherapy. The correlation between peripheral blood mononuclear cells, measured using fluorescence-activated cell sorting, was evaluated. Patients were divided into two groups according to the changes in PD-1(+)CD8(+) T-cell frequencies between day 0 and 7. They were categorized as increased or decreased PD-1(+)CD8(+) T-cell groups. The increased PD-1(+)CD8(+) T-cell group showed longer progression-free survival (PFS) and overall survival (OS) than the decreased PD-1(+)CD8(+) T-cell group (PFS: 8.7 months vs. 6.1 months, p = 0.007; OS: 20.7 months vs. 10.8 months, p = 0.003). The mean duration of response was significantly different between the groups (5.7 months vs. 2.5 months, p = 0.041). Multivariate analysis revealed that an increase in PD-1(+)CD8(+) T-cell frequency was an independent prognostic factor. We concluded that the early increase in PD-1(+)CD8(+) T-cell frequency is a potential predictor of favorable prognoses and durable responses in patients with advanced GC receiving chemotherapy.