Radiation combines with immune checkpoint blockade to enhance T cell priming in a murine model of poorly immunogenic pancreatic cancer

Open Biol. 2021 Nov;11(11):210245. doi: 10.1098/rsob.210245. Epub 2021 Nov 17.

Abstract

Radiation has been a pillar of cancer therapy for decades. The effects of radiation on the anti-tumour immune response are variable across studies and have not been explicitly defined in poorly immunogenic tumour types. Here, we employed combination checkpoint blockade immunotherapy with stereotactic body radiation therapy and examined the effect on tumour growth and immune infiltrates in subcutaneous and orthotopic mouse models of pancreatic cancer. Although immune checkpoint blockade and radiation were ineffective alone, their combination produced a modest growth delay in both irradiated and non-irradiated tumours that corresponded with significant increases in CD8+ T cells, CD4+ T cells and tumour-specific T cells as identified by IFNγ ELISpot. We conclude that radiation enhances priming of tumour-specific T cells in poorly immunogenic tumours and that the frequency of these T cells can be further increased by combination with immune checkpoint blockade.

Keywords: abscopal‌; immune checkpoint blockade; immunotherapy; pancreatic cancer; pancreatic ductal adenocarcinoma; radiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / radiation effects
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / radiation effects
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / pharmacology
  • Mice
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy*
  • Radiosurgery / methods*
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / radiation effects
  • Xenograft Model Antitumor Assays

Substances

  • Immune Checkpoint Inhibitors