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Regulation and modulation of antitumor immunity in pancreatic cancer

Nature Immunology volume 21, pages 1152–1159 (2020)Cite this article

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Abstract

Pancreatic ductal adenocarcinoma carries a dismal prognosis, and outcomes have improved little with modern therapeutics. Checkpoint-based immunotherapy has failed to elicit responses in the vast majority of patients with pancreatic cancer. Alongside tumor cell–intrinsic mechanisms associated with oncogenic KRAS-induced inflammation, the tolerogenic myeloid cell infiltrate has emerged as a critical impediment to adaptive antitumor immune responses. Furthermore, the discovery of an intratumoral microbiome and the elucidation of host–microbe interactions that curtail antitumor immunity also present opportunities for intervention. Here we review the mechanisms of immunotherapy resistance in pancreatic ductal adenocarcinoma and discuss strategies to directly augment T cell responses in parallel with myeloid cell– and microbiome-targeted approaches that may enable immune-mediated control of this malignancy.

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Fig. 1: Host–microbe interactions in PDA and tumor immunity.
Fig. 2: Myeloid cell recruitment, differentiation and targets in PDA.

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Authors and Affiliations

  1. S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY, USA

    Joshua Leinwand & George Miller

  2. Department of Cell Biology, New York University School of Medicine, New York, NY, USA

    George Miller

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Leinwand, J., Miller, G. Regulation and modulation of antitumor immunity in pancreatic cancer. Nat Immunol 21, 1152–1159 (2020). https://doi.org/10.1038/s41590-020-0761-y

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