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

Authors :
Stump CT
Roehle K
Manjarrez Orduno N
Dougan SK
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.

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