CHMP4A stimulates CD8+ T‐lymphocyte infiltration and inhibits breast tumor growth via the LSD1/IFNβ axis

Abstract

AbstractCD8+ T lymphocyte‐mediated immunity strategies have represented attractive weapons against breast cancer (BC) recently. However, the mechanisms underlying CD8+ T‐lymphocyte infiltration still remain obscure. Here, using bioinformatics analysis, we identified four hub prognostic genes related to CD8+ T‐lymphocyte infiltration (CHMP4A, CXCL9, GRHL2, and RPS29), among which CHMP4A was the most significant gene. High CHMP4A mRNA expression was significantly associated with longer overall survival (OS) in BC patients. Functional experiments showed that CHMP4A had the ability to promote CD8+ T‐lymphocyte recruitment and infiltration and suppressed BC growth in vitro and in vivo. Mechanistically, CHMP4A stimulates CD8+ T‐lymphocyte infiltration by downregulating LSD1 expression, leading to HERV dsRNA accumulation, and promoting IFNβ and its downstream chemokine production. Collectively, CHMP4A is not only a novel positive predictor for prognosis in BC but also a stimulator of CD8+ T‐lymphocyte infiltration regulated by the LSD1/IFNβ pathway. This study suggests that CHMP4A may be a novel target for improving the effectiveness of immunotherapy in patients with BC.