Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer

TLDR

Pancreatic ductal adenocarcinoma immune composition is poorly understood, and desmoplasia is thought to polarize this immunity. The study aims to comprehensively evaluate desmoplastic elements and T‑cell infiltration to clarify their roles and guide immune‑modulatory therapy optimization. The authors developed a novel computational imaging method that simultaneously evaluates eight markers for spatial analysis of distinct cell populations in a single tissue section. They found heterogeneous T‑cell infiltration, with cytotoxic T cells near cancer cells associated with better survival, and collagen‑I and αSMA+ fibroblasts not limiting T‑cell accumulation, indicating desmoplasia is not merely a physical barrier.

Abstract

Abstract The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section. We report a heterogeneous population of infiltrating T lymphocytes. Spatial distribution of cytotoxic T cells in proximity to cancer cells correlates with increased overall patient survival. Collagen-I and αSMA + fibroblasts do not correlate with paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a simple physical barrier. Further exploration of this technology may improve our understanding of how specific stromal composition could impact T-cell activity, with potential impact on the optimization of immune-modulatory therapies.