LDHB Mediates Histone Lactylation to Activate PD-L1 and Promote Ovarian Cancer Immune Escape

To investigate the effects of LDHB on lactylation of programmed cell death 1 ligand (PD-L1) and immune evasion of ovarian cancer. Ovarian cancer cells were transfected with LDHB siRNA and cultured with primed T cells. Cell proliferation and viability were measured by cell counting kit 8 (CCK-8) and colony formation assay. The production of immune factors was detected by enzyme-linked immunosorbent assay (ELISA). The histone lactylation and activity of PD-L1 promoter were measured by chromatin immunoprecipitation (ChIP)-qPCR assay and luciferase reporter gene assay, respectively. Knockdown of LDHB notably inhibited the growth, glucose uptake, lactate production, and ATP production of ovarian cancer cells. Knockdown of LDHB enhanced the killing effects of T cells, led to increased production of immune activation factors IL-2, TNF-α, and IFN-γ, as well as elevated the levels of granzyme B and perforin. Mechanical study identified that LDHB regulated the H3K18 lactylation (H3K18la) modification on PD-L1 promoter region to promote its expression. Overexpression of PD-L1 abolished the immune activation effects that induced by siLDHB. The LDHB modulated lactate production and the histone lactylation on PD-L1 promoter, which ultimately regulated its expression and participated in the immune evasion of ovarian cancer cells.