Skeletal Muscle Index, Tumor and Systemic Immunity, and Survival in Advanced Pancreatic Ductal Adenocarcinoma.

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.