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

Julienne L. Carstens, Pedro Correa De Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James P. Allison, Valerie S. Le Bleu, Raghu Kalluri

Research output: Contribution to journalArticlepeer-review

401 Scopus citations

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.

Original languageEnglish (US)
Article number15095
JournalNature communications
Volume8
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource
  • Flow Cytometry and Cellular Imaging Facility
  • Tissue Biospecimen and Pathology Resource
  • Clinical Trials Office

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