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Association of clinicopathological characteristics and baseline peripheral blood lymphocyte subsets with efficacy of first-line immunotherapy in advanced gastric cancer

Year: 2026

Type: article

Abstract: BACKGROUND: Immunotherapy has revolutionized treatment for advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC). However, identifying convenient biomarkers for predicting therapeutic efficacy remains challenging. This study investigated the association between clinicopathological characteristics and baseline peripheral blood lymphocyte subsets with efficacy of first-line chemotherapy combined with immune checkpoint inhibitors (ICIs) in proficient mismatch repair (pMMR) human epidermal growth factor receptor 2 (HER2)-negative advanced G/GEJC. METHODS: This retrospective study enrolled 97 patients with pMMR HER2-negative advanced G/GEJC receiving first-line chemotherapy combined with ICIs. Clinicopathological characteristics and peripheral blood lymphocyte subsets were collected. Overall survival (OS) and progression-free survival (PFS) were used to evaluate efficacy. The univariate and multivariate analyses were conducted using Cox regression analysis. RESULTS: Median PFS and OS were 5.9 and 15.2 months, respectively. Tumor location, Lauren classification, tumor differentiation, peritoneal metastases, neutrophil to lymphocyte ratio (NLR), and regulatory T cells (Tregs) as significantly associated with PFS. Well-differentiated tumor and higher Tregs independently predicted longer PFS. For OS, only higher NLR was an independent risk factor. Optimal cut-offs for NLR (3.5) and Tregs (10.1) stratified patients with significantly different PFS. A nomogram combining Tregs, NLR, peritoneal metastases, and tumor differentiation achieved superior predictive performance compared to PD-L1 CPS alone, with PFS AUC of 0.68-0.77 and OS AUC of 0.69-0.75. CONCLUSIONS: Clinicopathological characteristics and baseline peripheral lymphocyte subsets were significantly associated with efficacy of first-line chemotherapy combined with ICIs in pMMR HER2-negative advanced G/GEJC, highlighting the potential utility of integrating these accessible parameters for efficacy prediction.

Source: Discover Oncology

DOI: 10.1007/s12672-026-04444-z