PD-L1 levels, TP53 mutation profiles, and survival outcomes in pancreatic cancer differ by immune-nutritional status

Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits an immunosuppressive microenvironment coupled with malnutrition status. These features are instrumental in clinical management strategies for PDAC.

Immune-nutrition status of patients was evaluated by integrating systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI). Individuals were divided into SII-PNI Status positive (SPS⁺) group and SPS negative (SPS^-) group. Morphology of tissues was evaluated by hematoxylin-eosin (H&E) staining. Expression of PD-L1 and p53 was detected using immunohistochemistry (IHC).

In this study, 530 eligible patients (mean ± SD age, 60.5 ± 9.17 years, 296 males [55.8%], 74 SPS⁺ [14.0%]) were included. These patients exhibited a median survival of 24 months (1-, 3- and 5-year survival rate; 72.9%, 34.7% and 25.1%, respectively). In the multivariate analysis, independent indicators for outcomes were identified as tumor size, lymph node metastasis and SPS (all p <.01). After matching and adjusting, patients with SPS⁺ exhibited a notably reduced overall survival compared to those with SPS^- (14 vs. 25 months, p <.001), with hazard ratio (95% CI) of 1.79 (1.25-2.56). IHC revealed markedly elevated positive cell proportion of PD-L1 in SPS⁺ group (p <.01) and distinct p53 mutation patterns between SPS⁺ and SPS^- groups (p =.03). Morphology demonstrated a dissimilar trend of differentiation levels between the two groups (p =.08).

The findings suggest poorer outcome, higher PD-L1 expression and distinct p53 mutation status of patients with SPS⁺. These patterns may contribute to PDAC management and strategic deployment of immunotherapy and targeted therapy.