Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer.

ABSTRACT: The addition of aPD1 to 5-FU/platinum in advanced gastric cancer (GC) yields variable responses. To understand cooperativity between chemotherapy and immunotherapy, we previously reported a phase II trial sequentially adding pembrolizumab to 5-FU/platinum. In this study, we use single-cell RNA- and TCR-sequencing to analyze 66,813 T cells from primary tumor biopsies pre-treatment, post-chemotherapy, and post-immunotherapy in 33 patients. We observed greater abundance, persistence, and recruitment of T cells with predicted tumor-reactivity in patients with prolonged progression-free survival (slow progressors). Increased B cell abundance and predicted B cell to T cell interactions supported T cell memory and co-stimulation, providing a mechanism for increased abundance and persistence of pr

SUBMITTER: Wright SJ 

PROVIDER: S-EPMC12407690 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature