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

作者：Julienne L. Carstens, Pedro Corrêa de Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James Patrick Allison, Valerie S. LeBleu, Raghu K. Kalluri · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/ncomms15095 · 被引用次数：653 · 研究领域：Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research、Immunotherapy and Immune Responses

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.