BCG immunotherapy inhibits cancer progression by promoting the M1 macrophage differentiation of THP-1 cells via the Rb/E2F1 pathway in cervical carcinoma

Liu, Limin; Shi, Wenjuan; Xiao, Xiao; Wu, Xuemei; Hu, Haiyan; Yuan, Shixin; Liu, Kai; Liu, Zhihua

Bacillus Calmette-Guérin (BCG) immunotherapy increases macrophage polarization toward M1-type macrophages. In the present study, to identify the M1/M2 marker genes in the carcinogenesis and progression of cervical cancer, the microarray datasets GSE9750 and GSE7803 were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena browser. Survival analysis revealed that M1 markers (IL-12) were involved in anti-tumour progression, and M2 markers (IL-10) were involved in the carcinogenesis and invasion of cervical cancer. The expression of M1 markers (IL-12, inducible nitric oxide synthase and CD80) and M2 markers (IL-10 and arginase) was examined to determine whether BCG affects the polarization of macrophages and to elucidate the underlying mechanisms. The results revealed that BCG promoted macrophage polarization towards the M1 phenotype and enhanced the transition of M2 to M1 macrophages. The results also revealed that polarized M1 macrophages induced by BCG decreased the protein expression of phosphorylated (p-)retinoblastoma (Rb)/E2F transcription factor 1 (E2F1), inhibited the proliferation and promoted the apoptosis of HeLa cells. On the whole, these results demonstrated that BCG promoted the anti-tumour progression of M1 macrophages and inhibited the pro-tumour activation of M2 macrophages via the Rb/E2F1 signalling pathway in HeLa cells. This suggests the possibility of a direct translation of this combination strategy to clinical practice for the treatment of cervical cancer.