IMMUNE AND MOLECULAR CORRELATES OF RESPONSE TO IMMUNOTHERAPY REVEALED BY BRAIN-METASTATIC MELANOMA MODELS.

ABSTRACT: Despite the promising results of immune checkpoint blockade (ICB) therapy, outcomes for patients with brain metastasis (BrM) remain poor. Identifying resistance mechanisms has been hindered by limited access to patient samples and relevant preclinical models. Here, we developed two mouse melanoma BrM models that recapitulate the disparate responses to ICB seen in patients. We demonstrate that these models capture the cellular and molecular complexity of human disease and reveal key factors shaping the tumor microenvironment and influencing ICB response. BR1-responsive tumor cells express inflammatory programs that polarize microglia into reactive states, eliciting robust T cell recruitment. In contrast, BR3-resistant melanoma cells are enriched in neurological programs and exploit toleranc

SUBMITTER: Daugherty-Lopes A 

PROVIDER: S-EPMC11451731 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature