P38 blockade reverses the immune suppressive microenvironment in metastatic breast cancer

ABSTRACT: The study investigated the role of p38α in regulating the outcome of the immune-tumor interaction in metastatic breast cancer. Single-cell transcriptomic analysis of the immune-TME showed that pharmacological p38 inhibition (p38i) or tumor-specific inactivation of p38α by CRISPR/Cas9 (p38KO) resulted in a less exhausted and more activated CD8+ T cell phenotype. Moreover, the myeloid cells in the TME exhibited reduced expression of immune-suppressive factors and chemotactic receptors. Overall, this study highlights a previously unrecognized p38α-driven pathway that promotes an immune suppressive TME and that therapeutic blockade of p38α has important implications for improving antitumor immunity and patient outcomes.

ORGANISM(S): Mus musculus

PROVIDER: GSE282734 | GEO | 2025/11/23

REPOSITORIES: GEO