LAUSR

Introduction: Helicobactoer pylori (H. pylori) is one of the most important risk factors of gastric cancer (GC). However, the effects of Helicobacter pylori on the immune microenvironment and its potential roles in tumor immunotherapy responses is still lacking. Methods: We included 61 patients, 46 of whom received anti-PD-1/PD-L1 based immunotherapy. Patients’ samples at baseline were collected and examined with multiplex immunothistochemistry. Four detecting panels including 16 kinds of antibodies were used to label CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and their functional status. Immunotherapy-related overall survival (irOS) is the interval from the initiation of immunotherapy to death or the last following up. mmunotherapy-related progression-free survival (irPFS) is the interval from the initiation of immunotherapy to disease progression or the last following up. The Student’s t test is used to compared the average density of immune cells. The Chi-squared test was used to compare the objective response rate (ORR) between two groups. Results: H. pylori-positive rate was 29/61. In 46 patients received immunotherapy, 23 patients were infected with H. pylori. There was a increasing trend for the density of CD8+ T cells, B cells, and neutrophils in H. pylori-positive patients compared with negative group. We observed that the densities of total CD4+ T cells, CD4+PD-L1+, and CD4+CTLA-4+ T cells, were higher in H. pylori-positive group compared with negative group (522.58 vs. 268.77/mm^2, P=0.020, 118.94 vs. 265.98/mm^2, P=0.0091; 61.30 vs. 18.56/mm^2, P=0.035). In addition, STING positive macrophages (CD68+STING+ cells) were also enriched in H. pylori-positive group than negative group (138.45 vs. 44.15/mm^2, P=0.0012). Next, we found H. pylori-positive patients harbored higher ORR than negative group (47.62% vs. 17.39%, P=0.032). However, there were no significant difference of irPFS and irOS between positive and negative group (median irPFS: 5.97 vs. 6.83 months, hazard ratio: 1.02, P=0.96; median irOS: 12.83 vs. 10.97 months, hazard ratio: 0.855, P=0.59). Conclusions: We observed the enrichment of total CD4+ T cells, CD4+PD-L1+ T cells, CD4+CTLA-4+ T cells, and CD68+STING+ cells in H. pylori-positive patients, indicating the combination of anti-CTLA-4 or STING may enhance the efficacy of immunotherapy in H. pylori-positive GC. Citation Format: Keren Jia, Yang Chen, Xiaoyi Chong, Yilin Li, Jiajia Yuan, Yanyan Li, Xiaotian Zhang, Jian Li, Lin Shen. The immune features of Helicobactor pylori-positive gastric cancer provides insights into immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5902.