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Radiation combines with immune checkpoint blockade to enhance T cell priming in a murine model of poorly immunogenic pancreatic cancer.
- Source :
-
Open biology [Open Biol] 2021 Nov; Vol. 11 (11), pp. 210245. Date of Electronic Publication: 2021 Nov 17. - Publication Year :
- 2021
-
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.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes radiation effects
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes radiation effects
Cell Line, Tumor
Disease Models, Animal
Humans
Immune Checkpoint Inhibitors pharmacology
Mice
Pancreatic Neoplasms immunology
Treatment Outcome
Tumor Microenvironment drug effects
Tumor Microenvironment radiation effects
Xenograft Model Antitumor Assays
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes metabolism
Immune Checkpoint Inhibitors administration & dosage
Pancreatic Neoplasms therapy
Radiosurgery methods
Subjects
Details
- Language :
- English
- ISSN :
- 2046-2441
- Volume :
- 11
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Open biology
- Publication Type :
- Academic Journal
- Accession number :
- 34784792
- Full Text :
- https://doi.org/10.1098/rsob.210245