磷酸甘油酸变位酶1通过调控CD8+T细胞浸润及功能影响肺癌免疫微环境OA北大核心

Objective:To investigate the regulatory role of phosphoglycerate mutase 1(PGAM1)in lung cancer LLC cell proliferation and migration,and to explore its impact on the function and infiltration of CD8* T cells within the tumor microenvironment.Methods:LLC cells were infected with shPGAM1 and shNC lentiviruses,and stable cell lines were established and designated as the shPGAM1 group and the NC group,respectively.WB and qPCR were used to assess the protein and mRNA expression levels of PGAM1 in both groups.Cell proliferation and migration after PGAM1 knockdown were assessed using the CCK-8 assay and real-time cell analyzer.Flow cytometry was employed to detect the expression of CD8* T-cell functional receptors(TIM-3,PD-1,GrzmB,Ki67)after co-culture with cells from each group in vitro.A subcutaneous LLC xenograft model was established in mice to examine the effect of PGAM1 on tumor growth,and flow cytometry was used to evaluate the impact of PGAM1 knockdown on CD8* T cell infiltration in the tumor microenvironment.Results:The protein and mRNA expression levels of PGAM1 were significantly reduced in the shPGAM1 group compared with the NC group.Knockdown of PGAM1 significantly reduced the proliferation and migration of LLC cells(P<0.000 1 or P<0.05).After co-culture with shPGAM1 cells,the expression of exhaustion markers(TIM-3,PD-1)on CD8* T cells decreased notably(P<0.000 1 or P<0.01).Knockdown of PGAM1 significantly inhibited tumor growth and increased CD8* T cell infiltration in tumor tissues(P<0.000 1).Conclusion:Targeted knockdown of PGAM1 inhibits tumor cell proliferation and migration,reduces the expression of exhaustion markers on CD8* T cells,and enhances T cell infiltration within tumors,thereby exerting dual effects on tumor growth and antitumor immunity.