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

Nat Commun. 2017 Apr 27:8:15095. doi: 10.1038/ncomms15095.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Collagen Type I / metabolism
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Immunohistochemistry / methods
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Mice
  • Middle Aged
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Spatial Analysis
  • Spectrum Analysis
  • Survival Rate
  • T-Lymphocytes / pathology
  • T-Lymphocytes, Cytotoxic / pathology*
  • Tissue Array Analysis

Substances

  • ACTA2 protein, human
  • Actins
  • Collagen Type I