Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

ABSTRACT: The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N⁶-methyladenosine (m⁶A) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood. Here, we report that METTL3 elevates expression of pro-tumorigenic chemokines including CXCL1, CXCL5, and CCL20, and destabilizes PD-L1 mRNA in an m⁶A-dependent manner, thereby shaping a non-inflamed TME. Thus, inhibiting METTL3 re

SUBMITTER: Yu H 

PROVIDER: S-EPMC10954589 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature