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bioRxiv · 10.1101/2023.07.28.551021

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

Sanchez-Pupo, R. E.·Finch, G.·Johnston, D. E.·Craig, H.·Abdo, R.·Barr, K. J.·Kerfoot, S. M.·Dagnino, L.·Penuela, S.
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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: 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, 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.

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Sanchez-Pupo, R. E., Finch, G., Johnston, D. E., Craig, H., Abdo, R., Barr, K. J., Kerfoot, S. M., Dagnino, L., Penuela, S.. 2023-07-29. Global Pannexin 1-deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model.. https://doi.org/10.1101/2023.07.28.551021

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