The tumor microenvironment disarms CD8⁺ T lymphocyte function via a miR-26a-EZH2 axis.

ABSTRACT: One of the most important factors that limit the potency of CD8⁺ cytotoxic T lymphocyte (CTL) responses is the tumor microenvironment (TME). Here, we provide evidence that miR-26a is a negative regulator of CTL function in the TME. Specifically, we identified miR-26a as a crucial suppressor gene in CTLs from the TME, as we found that, miR-26a expression was elevated in CTLs to respond to TME secretome stimulation. CTLs from miR-26a-transgenic mice showed impaired IFNγ and granzyme B production in response to their cognate antigen. Conversely, we found that miR-26a inhibition in CTLs could effectively increase the cytotoxicity and suppress tumor growth. Mechanically, we identified EZH2 as a direct target of miR-26a. miR-26a and EZH2 expression were found to be inversely correlate

SUBMITTER: Long H 

PROVIDER: S-EPMC5214597 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature