Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Jiang Liu; Degan Liu; Guangyin Hu; Jingjing Wang; Dadong Chen; Chuanjun Song; Yin Cai; Chentong Zhai; Wenjing Xu

doi:10.1186/s12935-023-03137-9

Circulating memory PD-1⁺CD8⁺ T cells and PD-1⁺CD8⁺T/PD-1⁺CD4⁺T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Cancer Cell Int. 2023 Nov 16;23(1):274. doi: 10.1186/s12935-023-03137-9.

Authors

Jiang Liu¹, Degan Liu², Guangyin Hu², Jingjing Wang², Dadong Chen², Chuanjun Song², Yin Cai², Chentong Zhai², Wenjing Xu³

Affiliations

¹ Department of Oncology, The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University, 419 Ying Wu Nan Road, Xinghua, 225700, Jiangsu, People's Republic of China. liujiang8901@163.com.
² Department of Oncology, The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University, 419 Ying Wu Nan Road, Xinghua, 225700, Jiangsu, People's Republic of China.
³ Department of Oncology, The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University, 419 Ying Wu Nan Road, Xinghua, 225700, Jiangsu, People's Republic of China. 2007xuwenjing@163.com.

Abstract

Background: Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8⁺ T cells and CD8⁺T/CD4⁺T cell ratio in advanced gastric cancer patients receiving immunotherapy.

Methods: A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier methods and Cox proportional hazards regression models.

Results: The optimal cutoff values for percentages of CD8⁺ T cells, naive CD8⁺ T cells (CD8⁺ Tn) and memory CD8⁺ T cells (CD8⁺ Tm) expressing programmed cell death -1(PD-1) as well as PD-1⁺CD8⁺T/PD-1⁺CD4⁺T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8⁺ T and CD8⁺ Tm expressing PD-1 as well as PD-1⁺CD8⁺T/PD-1⁺CD4⁺T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8⁺ T and CD8⁺ Tm expressing PD-1 as well as PD-1⁺CD8⁺T/PD-1⁺CD4⁺T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy.

Conclusion: The circulating memory PD-1⁺CD8⁺ T cells and PD-1⁺CD8⁺T/PD-1⁺CD4⁺T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1⁺CD8⁺ T cells and PD-1⁺CD8⁺T/PD-1⁺CD4⁺T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence.

Keywords: CD8+T/CD4+T cell ratio; Gastric cancer; Immune checkpoint inhibitors; Immunotherapy; Memory CD8+ T cells; Predictive biomarkers.