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Updated: Dec 11, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
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Regulation and modulation of antitumor immunity in pancreatic cancer

Joshua Leinwand1, George Miller2,3

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

Nature Immunology
|August 19, 2020
PubMed

Insights

Pancreatic cancer immunotherapy resistance stems from tumor inflammation, myeloid cells, and the microbiome. New strategies targeting these factors may improve immune-mediated control of pancreatic ductal adenocarcinoma.

Area of Science:

  • Oncology
  • Immunology
  • Microbiome research

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with limited therapeutic advancements.
  • Checkpoint immunotherapy has shown minimal efficacy in most pancreatic cancer patients.
  • Tumor-intrinsic factors, including KRAS-induced inflammation and tolerogenic myeloid cells, hinder anti-tumor immunity.

Purpose of the Study:

  • To review mechanisms of immunotherapy resistance in PDAC.
  • To discuss strategies for augmenting T cell responses.
  • To explore myeloid cell- and microbiome-targeted approaches for immune-mediated control.

Main Methods:

  • Literature review of immunotherapy resistance mechanisms in PDAC.
  • Analysis of tumor-intrinsic factors, myeloid cell infiltrates, and intratumoral microbiome.
  • Discussion of potential therapeutic interventions.

Main Results:

  • Oncogenic KRAS-induced inflammation and tolerogenic myeloid cells are key barriers to adaptive immunity in PDAC.
  • The intratumoral microbiome and host-microbe interactions can suppress anti-tumor immune responses.
  • Multiple mechanisms contribute to immunotherapy resistance in pancreatic cancer.

Conclusions:

  • Overcoming PDAC immunotherapy resistance requires addressing tumor-intrinsic mechanisms, myeloid cell populations, and the gut microbiome.
  • Combined strategies targeting T cell responses alongside myeloid and microbiome modulation hold promise for effective cancer control.
  • Further research into these multifaceted interactions is crucial for developing novel pancreatic cancer therapies.

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