Transcriptional profiles of UVB-induced BRAFV600E mouse melanoma tumors with or without p38α (whole tumor, CD45⁺ and CD45⁻ populations)

Using a conditional UVB-induced melanoma mouse model (Tyr::CreERT2;BrafCA/CA and Tyr::CreERT2;BrafCA/CA;p38αlox/lox), we investigated how the loss of the stress kinase p38α in melanocytes affects tumor development and immune evasion. We performed transcriptional profiling on whole tumors, as well as on separated CD45⁺ (immune) and CD45⁻ (tumor/stroma) populations.

Comparative transcriptomic analysis revealed that p38α deficiency reprograms both tumor and immune compartments, promoting immune-stimulatory gene expression and reducing immunosuppressive and pro-tumorigenic signals. Many of the genes modulated by p38α loss are associated with an improved response to immune checkpoint blockade in melanoma patients. These findings underscore the role of p38α in shaping an immunosuppressive and pro-tumorigenic microenvironment, suggesting p38α as a potential target to enhance the efficacy of immunotherapy.