Global Pannexin 1-deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

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 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: Braf CA , Pten loxP , Tyr::CreER T2 (BPC). We found that deleting the Panx1 gene in mice does not reduce BRAF(V600E)/Pten-driven primary tumor formation or improve survival. However, BPC- Panx1 −/- mice tumors exhibited a significant increase in infiltration of CD8 + T lymphocytes with no changes in the expression of early T cell activation marker CD69, LAG-3 checkpoint receptor or PD-L1 in tumors when compared to BPC- Panx1 +/+ genotype. Our results suggest that although a 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.