Impact of regulatory t cells in peripheral blood on pathological complete response in patients with locally advanced gastric or gastroesophageal junction cancer undergoing neoadjuvant chemoimmunotherapy.
Authors: Zhao Lingdi , Liu Xiao , Chen Guanglong , Qin Peng , Ma Baozhen , Jiang Zhiqiang , Huang Jinxi , Li Zhi , Zhang Yong , Wang Zibing , Gao Quanli 
Published: July 2024

e16081 Background: Neoadjuvant chemotherapy has become the standard treatment for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer. With the widely clinical application of immune checkpoint inhibitors, represented by anti-PD-1 antibodies, an increasing number of patients with locally advanced G/GEJ cancer are undergoing neoadjuvant chemoimmunotherapy. However, there is currently no effective predictive marker for neoadjuvant chemoimmunotherapy in locally advanced G/GEJ cancer. We explored the role of peripheral blood regulatory T (Treg) cells in patients with locally advanced G/GEJ cancer. Methods: We retrospectively analyzed lymphocyte subpopulations before and after treatment in patients with locally advanced G/GEJ cancer who received neoadjuvant chemotherapy combined with anti-PD-1 antibodies and curative surgery. Inclusion criteria were: 1) Pathologically confirmed adenocarcinoma of the G/GEJ; 2) Clinically staged as gastric cT3-4 or N+ without distant metastasis by enhanced CT and endoscopic ultrasound examination; 3) Patients requiring neoadjuvant treatment according to gastric cancer multidisciplinary team decisions; 4) Receipt of neoadjuvant treatment with chemotherapy combined with PD-1 antibodies; 5) Completion of 3-4 cycles of treatment; 6) Underwent curative resection; 7) Lymphocyte subpopulation testing performed before the first and second cycles. Results: From July 1, 2020, to May 31, 2023, 85 patients were included. All 85 patients underwent D2 radical surgery and achieved R0 resection, with 21 patients achieving pathological complete response (pCR), resulting in a pCR rate of 24.7% (95% confidence interval (CI) 15.3-34.1%). There were no statistically significant differences in baseline characteristics between the pCR and non-pCR groups. There were no statistically significant differences in lymphocyte subpopulations between the baseline pCR and non-pCR patient groups. After one cycle of treatment (before the second cycle), there were statistically significant differences in lymphocytes, T lymphocytes, and Treg cells between the two groups. Further analysis of the absolute changes in lymphocyte subpopulations before and after one cycle of treatment revealed a greater decrease in Treg cells in the pCR group. Based on the increase or decrease in Treg cells after one cycle of treatment, the 85 patients were divided into Treg cell increase and decrease groups. The pCR rate was 11.4% (4/35, 95% CI 0.3-22.5%) in the Treg cell increase group and 34% (17/50, 95% CI 20.4-47.6%) in the Treg cell decrease group, with a statistically significant difference between the two groups ( P= 0.022). Conclusions: In locally advanced G/GEJ cancer, changes in Treg cells after one cycle of neoadjuvant treatment may serve as a predictive marker for achieving pCR.