The impact of combined immunotherapy on the cellular composition of the tumor microenvironment in patients with gastric carcinoma

Objective. To evaluate the impact of combined anti-PD-1 immunotherapy on the cellular composition of the tumor microenvironment in patients with gastric cancer. Material and methods. The study included 9 patients with morphologically confirmed gastric adenocarcinoma (stages T2-4N0-1M0) and positive PD-L1 status (CPS >1). All patients received 8 courses of preoperative chemotherapy according to the FLOT regimen, combined with additional immunotherapy using pembrolizumab (400 mg every 6 weeks). Changes in the tumor microenvironment were assessed using multicolor immunofluorescence followed by quantitative analysis of the proportions of CD8+ cytotoxic T-lymphocytes, CD20+ B-lymphocytes, CD163+ macrophages, and FoxP3+ regulatory T-cells. Results. A statistically significant increase in the number of CD8+ T-lymphocytes (from 3.18% to 6.23%, p=0.0391) and, in particular, their PD-1-expressing subpopulation (from 0.00% to 0.22%, p=0.0156) was observed, while the numbers of CD20+, CD163+, and FoxP3+ cells remained unchanged. As a result, the CD8+/FoxP3+ cell ratio significantly increased during combined anti-PD-1 immunotherapy (from 0.69 to 3.22, p=0.0039). Additionally, associations were identified between immune parameters and clinicopathological characteristics, suggesting that gender and tumor stage may influence the immune response. Conclusion. The obtained data indicate a remodeling of the tumor microenvironment under the influence of anti-PD-1 therapy, which potentially enhances the antitumor immune response and opens prospects for further optimization of gastric cancer treatment.