Targeting the atypical chemokine receptor 2 (<i>Ackr2</i>) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model.

ABSTRACT: Immune checkpoint blockade (ICB) therapies, such as anti-PD-1, have transformed cancer treatment, but many patients do not respond due to a non-inflammatory tumor microenvironment (TME). Here, we investigated the impact of targeting Atypical Chemokine Receptor 2 (ACKR2), which scavenges key chemokines involved in immune cell recruitment, on the improvement of anti-PD-1-based therapy. In a melanoma mouse model, we demonstrated that Ackr2 inhibition increases the release of proinflammatory chemokines CCL5 and CXCL10 and enhances the infiltration of NK cells, activated CD8+ and CD4+ effector T cells while reducing regulatory T cells (Tregs) in the TME. Targeting Ackr2 led to tumor growth inhibition, improved survival, and enhanced response to anti-PD-1 therapy. In BRAF- a

SUBMITTER: Noman MZ 

PROVIDER: S-EPMC12013441 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature