A Potential Biomarker of Dynamic Change in Peripheral CD45RA(−)CD27(+)CD127(+) Central Memory T Cells for Anti-PD-1 Therapy in Patients with Esophageal Squamous Cell Carcinoma

SIMPLE SUMMARY: In order to develop a biomarker predicting the efficacy of chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT) for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with each therapy. The frequencies of PD-1(+) or TIM-3(+)CD4(+) T cells were significantly higher in patients with cStage IV. PD-1(+)CD4(+) and TIM-3(+)CD8(+) T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4(+) and CD8(+) central memory T cells (T(CM)) were significantly decreased during NT in the progressive disease group. Taken together, the alteration in frequency of T(CM) during NT may be a biomarker to predict its therapeutic response in ESCC patients. ABSTRACT: In order to develop a biomarker predicting the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). Fifty-five ESCC patients were enrolled in this study, and peripheral blood samples were collected before and after CT or CRT and during NT. Frequencies of memory, differentiated, and exhausted T cells were evaluated using flow cytometry among cStages, treatment strategies, pathological responses of CT/CRT, and during NT. The frequencies of PD-1(+) or TIM-3(+)CD4(+) T cells were significantly higher in patients with cStage IV. PD-1(+)CD4(+) and TIM-3(+)CD8(+) T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4(+) and CD8(+) CD45RA(−)CD27(+)CD127(+) central memory T cells (T(CM)) were significantly decreased during the course of NT in the progressive disease group. Taken together, the alteration in frequency of CD45RA(−)CD27(+)CD127(+) T(CM) during NT may be a biomarker to predict its therapeutic response in ESCC patients.