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The tumor microenvironment disarms CD8 T lymphocyte function via a miR-26a-EZH2 axis.
- Source :
-
OncoImmunology . 2016, Vol. 5 Issue 12, p1-1. 1p. - Publication Year :
- 2016
-
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 correlated in CTLs, and the inhibition of EZH2 in CTLs impairs CTL function. These functional correlations were validated in a cohort of non-small cell lung cancer patients, indicating that the miR-26a-EZH2 axis is clinically relevant. Our findings suggested that miR-26a silencing as a novel strategy to improve the efficacy of CTL-based cancer immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TUMOR microenvironment
*T cells
Subjects
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 5
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 120643813
- Full Text :
- https://doi.org/10.1080/2162402X.2016.1245267