In recent years, the therapeutic effect of monoclonal antibodies against programmed cell death protein-1 (PD-1) in patients with locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer has been confirmed in many studies. The exploration and discovery of new biomarker combinations based on tumor characteristics and tumor microenvironment help screen superior patients and realize precise immunotherapy. As an evaluation index of immunonutritional status, the prognostic nutritional index (PNI) is low cost, simple and easy to obtain, and effective in determining the prognosis of tumor patients. We selected 268 consecutive AGC patients who were treated with ICI therapy from December 2014 to May 2021. We measured their pretreatment of the PNI levels and performed univariate and multivariate Cox regression analyses of progression-free survival (PFS) or overall survival (OS) after ICI therapy. The low pretreatment PNI level of AGC patients was significantly correlated with shorter PFS (p < 0.001) and OS (p < 0.001) after ICI treatment. In univariate and multivariate analyses of the associations between PNI and OS or PFS, PNI is an independent prognostic factor for PFS (HR = 1.511; 95%CI 1.154–1.977; p = 0.003) and OS (HR = 1.431; 95%CI 1.049–1.951; p = 0.024), respectively. Notably, decreased PNI during treatment with ICIs was associated with early relapse and death. Pretreatment with PNI might help to identify AGC patients who will obtain a survival benefit from ICI therapy.

Hyponatremia, a prevalent electrolyte imbalance among tumor patients, has often been overlooked regarding its prognostic significance for immunotherapy. In this study, we delved into the prognostic ramifications of hyponatremia in advanced gastric cancer (AGC) patients undergoing immunotherapy. Enrolling AGC patients diagnosed between December 2014 and May 2021, we extracted pertinent data from electronic medical records, with a median follow-up of 35.8 months. Kaplan-Meier curves illuminated patients' progression-free survival (PFS) and overall survival (OS), while survival disparities were tested using the Mantel-Haenszel log rank test. COX and logistic regressions were employed to scrutinize the correlation between serum sodium levels and prognosis in 268 AGC patients, both at baseline and during treatment. Notably, patients with hyponatremia exhibited shorter PFS (4.7 vs 2.1 months, p = .001*) and OS (12.5 vs 3.9 months, p < .001*). Serum sodium emerged as an independent prognostic factor for both PFS (HR = 1.773; 95% CI 1.067-2.945; p = .001*) and OS (HR = 1.773; 95% CI 1.067-2.945; p = .003*). Subgroup analysis revealed that AGC patients with hyponatremia derived no benefit from immunotherapy in terms of PFS and OS. Strikingly, a decrease in serum sodium during immunotherapy was associated with early relapse and mortality. Based on these findings, we hypothesize that hyponatremia portends poor prognostic outcomes in AGC patients treated with immunotherapy and may serve as a valuable prognostic biomarker. However, further large-scale prospective studies are warranted to validate these observations.

Background: This study investigated relationships between the skeletal muscle index (SMI) and the tumor immune microenvironment (TIME), peripheral immune phenotypes, and serum biomarkers in advanced pancreatic ductal adenocarcinoma (PDAC) and evaluated the prognostic significance of these parameters. Methods: A retrospective analysis of 119 advanced PDAC patients was performed. Sarcopenia was diagnosed using sex‐specific SMI cut‐offs from baseline L3‐level computed tomography (CT) images. The TIME was characterized by multiplex immunofluorescence (mIF; n = 31), peripheral immunity by flow cytometry, and serum biomarkers by routine testing. Associations with SMI were examined using Spearman correlation; prognostic relevance was assessed using Cox proportional hazards models. Results: Sarcopenia (56/119, 47.1%) was associated with shorter progression‐free survival (PFS) (8.83 vs. 12.03 months, p = 0.016) and overall survival (OS) (10.20 vs. 17.33 months, p = 0.014). SMI correlated most strongly with stromal CD8 ⁺ T cells ( ρ = 0.52), stromal total T cells ( ρ = 0.52), and stromal M2 macrophages ( ρ = 0.50) in the TIME; with circulating Th2‐like cells ( ρ = −0.58) and CD4 ⁺ memory T cells ( ρ = 0.45) peripherally; and with hemoglobin ( ρ = 0.32) among serum markers. In multivariable Cox regression, stromal CD4 ⁺ Treg percentage independently predicted OS (hazard ratio [HR] = 7.60, 95% confidence interval [CI] 1.60–36.22, p = 0.011), stromal CD56dim natural killer (NK)‐cell density predicted PFS (HR = 1.015, 95% CI 1.001–1.028, p = 0.031), and the lymphocyte‐to‐monocyte ratio (LMR) predicted both PFS (HR = 0.86, p = 0.023) and OS (HR = 0.83, p = 0.009). No peripheral lymphocyte subset reached prognostic significance. Conclusion: SMI is broadly associated with local and systemic immune phenotypes in advanced PDAC. Stromal CD4 ⁺ regulatory T cells (Tregs), CD56dim NK cells, and LMR carry independent prognostic information and may complement body‐composition assessment.