Role of β-2 microglobulin gene in the progression of breast cancer and its impact on the sensitivity to PD-L1 inhibitors

LIN Yuhong; ZHUANG Wanzhen; WANG Yuanyuan; LIU Jie; WANG Xiaoxian; CHEN Yong; ZHOU Xiaoyan

doi:10.13431/j.cnki.immunol.j.20250119

Abstract：Objective To investigate the role of β-2 microglobulin(B2M)gene in breast cancer progression and its impact on the sensitivity to programmed death-ligand 1(PD-L1)inhibitors.Methods RNA sequencing data of breast cancer were downloaded from The Cancer Genome Atlas(TCGA)database.B2M expression was detected in 1,121 samples,the correlation between B2M and PD-L1 gene expression was systematically analyzed.Mouse breast cancer cells(4T1 cells)were selected to establish B2M knockdown 4T1 cells(B2M KD 4T1 cells),so as to explore the effects of B2M expression on PD-L1 levels and cell functions.A subcutaneous tumor model was established with B2M KD 4T1 cells via in vivo experiments and treated with PD-L1 inhibitors,to evaluate the impact of the B2M gene on immune cell infiltration and therapeutic sensitivity.Results The gene expression levels of B2M and PD-L1 were elevated in breast cancer cells.In vitro functional experiments confirmed that B2M knockdown could significantly inhibit the proliferation of 4T1 cells,accompanied by enhanced apoptosis and decreased PD-L1 expression.PD-L1 had independent biological functions,which could promote the proliferation,invasion and migration of 4T1 cells while inhibiting apoptosis,thus exhibiting similar functional tendencies and regulatory outcomes similar to those of B2M.In vivo tumor-bearing experiments showed that the tumor volume formed by B2M knockdown 4T1 cells in mice was significantly suppressed,and showed no significant response to PD-L1 inhibitor treatment.Conclusion B2M knockdown may inhibit the proliferation of breast cancer cells by reducing immune cell recruitment and PD-L1 expression,and concomitantly impair the sensitivity of these cells to PD-L1 inhibitors.