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

Author

Listed:
  • Julienne L. Carstens

    (Metastasis Research Center, The University of Texas MD Anderson Cancer Center)

  • Pedro Correa de Sampaio

    (Metastasis Research Center, The University of Texas MD Anderson Cancer Center)

  • Dalu Yang

    (The University of Texas MD Anderson Cancer Center
    Rice University)

  • Souptik Barua

    (The University of Texas MD Anderson Cancer Center
    Rice University)

  • Huamin Wang

    (The University of Texas MD Anderson Cancer Center)

  • Arvind Rao

    (The University of Texas MD Anderson Cancer Center
    Rice University
    The University of Texas MD Anderson Cancer Center)

  • James P. Allison

    (The University of Texas MD Anderson Cancer Center)

  • Valerie S. LeBleu

    (Metastasis Research Center, The University of Texas MD Anderson Cancer Center)

  • Raghu Kalluri

    (Metastasis Research Center, The University of Texas MD Anderson Cancer Center
    Rice University
    Baylor College of Medicine)

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.

Suggested Citation

  • Julienne L. Carstens & Pedro Correa de Sampaio & Dalu Yang & Souptik Barua & Huamin Wang & Arvind Rao & James P. Allison & Valerie S. LeBleu & Raghu Kalluri, 2017. "Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15095
    DOI: 10.1038/ncomms15095
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    Cited by:

    1. Darci Phillips & Magdalena Matusiak & Belén Rivero Gutierrez & Salil S. Bhate & Graham L. Barlow & Sizun Jiang & Janos Demeter & Kimberly S. Smythe & Robert H. Pierce & Steven P. Fling & Nirasha Ramch, 2021. "Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Yang Chen & Keren Jia & Yu Sun & Cheng Zhang & Yilin Li & Li Zhang & Zifan Chen & Jiangdong Zhang & Yajie Hu & Jiajia Yuan & Xingwang Zhao & Yanyan Li & Jifang Gong & Bin Dong & Xiaotian Zhang & Jian , 2022. "Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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