Affiliation:
1. Department of Anatomy and Cell Biology Western University London Canada
2. Department of Microbiology and Immunology Western University London Canada
3. Department of Physiology and Pharmacology Western University London Canada
4. Division of Experimental Oncology, Department of Oncology, Schulich School of Medicine and Dentistry Western University London Canada
Abstract
Immunotherapies for malignant melanoma seek to boost the anti‐tumoral response of CD8+ T cells, but have a limited patient response rate, in part due to limited tumoral immune cell infiltration. Genetic or pharmacological inhibition of the pannexin 1 (PANX1) channel‐forming protein is known to decrease melanoma cell tumorigenic properties in vitro and ex vivo. Here, we crossed Panx1 knockout (Panx1−/−) mice with the inducible melanoma model BrafCA, PtenloxP, Tyr::CreERT2 (BPC). We found that deleting the Panx1 gene in mice does not reduce BRAF(V600E)/Pten‐driven primary tumor formation or improve survival. However, tumors in BPC‐Panx1−/− mice exhibited a significant increase in the infiltration of CD8+ T lymphocytes, with no changes in the expression of early T‐cell activation marker CD69, lymphocyte activation gene 3 protein (LAG‐3) checkpoint receptor, or programmed cell death ligand‐1 (PD‐L1) in tumors when compared to the BPC‐Panx1+/+ genotype. Our results suggest that, although Panx1 deletion does not overturn the aggressive BRAF/Pten‐driven melanoma progression in vivo, it does increase the infiltration of effector immune T‐cell populations in the tumor microenvironment. We propose that PANX1‐targeted therapy could be explored as a strategy to increase tumor‐infiltrating lymphocytes to boost anti‐tumor immunity.
Funder
Canadian Institutes of Health Research