MAPK/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy.

ABSTRACT:

Background

Glioblastoma (GB) remains a formidable challenge in neuro-oncology, with immune checkpoint blockade (ICB) showing limited efficacy in unselected patients. We previously recently established that MAPK/ERK signaling is associated with overall survival following anti-PD-1 and anti-CTLA-4 treatment in recurrent GB. However, the causal relationship between MAPK/ERK signaling and susceptibility to ICB, as well as the mechanisms underlying this association, remain poorly understood.

Method

We conducted in vivo kinome-wide CRISPR/Cas9 screenings in murine gliomas to identify key regulators of susceptibility to anti-PD-1 and CD8⁺ T cell responses and performed survival studies to validate the most relevant genes. Additionally, paired single cell RNA-seque

SUBMITTER: Kim KS 

PROVIDER: S-EPMC11429708 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature