Abstract 563P
Background
Although macrophages have been identified as a regulator of tumor immunity and immunotherapy in many cancer types, with M2-polarized macrophages being reputed to facilitate tumor progression, the mechanisms of M1-M2 transition in human papillomavirus (HPV) carcinogenesis and tumor immunity remained to be determined.
Methods
Single-cell transcriptome data from cervical cancer (n=8198), normal cervix (n=19033), and peripheral blood mononuclear cells (n=32923) were analyzed to identify the expression patterns of macrophages. RNA-seq data from datasets were integrated to explore the M2-to-M1 transition of macrophages in cervical carcinoma. In addition, survival analysis and sub-expression analysis of M0/M1/M2 cells were performed to validate the molecular correlation between AIF1 and the status of macrophages. Furthermore, in vitro and in vivo assays were performed to testify molecular functions of AIF1 in M2-to-M1 transition.
Results
Single-cell transcriptome analysis identified that AIF1 was a specific marker of macrophages in cervical cancer, normal cervix, and peripheral blood mononuclear cells, which was positively associated with M1 status and negatively associated with M2 status in cervical cancer. Cancer survival analysis revealed that high expression of AIF1 was correlated with favorable disease outcomes, with the same tendency that high M1 expression patterns showed favorable disease outcomes in cervical cancer (Log-rank P = 0.02). In vitro and in vivo, high expression of AIF1 in macrophages promoted M2-to-M1 transition via regulating the expression of NF-κB and TNF-α, which restrains the expression of HPV-E6/E7 in cervical cancer cells. Also, high expression of AIF1 in macrophages facilitated immune cell infiltration in the tumor microenvironment. Then, high expression of AIF1 in macrophages not only restrained cell proliferation and migration but also suppressed the progression of cervical carcinoma in vivo.
Conclusions
Overall, single-cell transcriptome analysis identified that AIF1 was associated with the M2-to-M1 transition of macrophages and was responsible for down-regulation of HPV-E6/E7 in cervical carcinoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.