全球 pannexin 1 缺失在 BRAF/Pten 小鼠黑色素瘤模型中增加 TIL（肿瘤浸润淋巴细胞）

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 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, 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.