Introduction/Background The C-X-C motif chemokine ligands (CXCLs)- C-X-C motif chemokine receptor 2 (CXCR2) axis might play a critical role in cervical caner microenvironment. In this study, we aimed to check the expression profile of the CXCLs-CXCR2 axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis.

Methodology Available RNA-sequencing data based on bulk tissues and single-cell RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies.

Results Results showed that except neutrophils, CXCR2 mRNA expression is quite limited in other types of cells in the cervical tumor microenvironment. In comparison, CXCLs that bind to CXCR2 are mainly expressed by tumor cells. CXCR2 expression level is not related the overall survival of patients with cervical cancer. In comparison, CXCL1, 2, 3, 5, 6 and 8, which are consistently associated with neutrophil infiltration are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impaired SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5,or CXCL8 neutralized conditioned medium from SiHa cells had much weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. In comparison, conditioned medium of TANs (tumor-associated neutrophils) drastically enhance cervical cancer cell growth in vitro. Hela and SiHa cells co-administrated with TANs grew faster in vivo, compared to the tumor cells inoculated alone.

Conclusion In conclusion, this study revealed that CXCLs-CXCR2 axis play a critical role in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

Disclosures This study was funded by the 2021 Fujian Provincial Science and Technology Innovation Joint Project (NO:2021Y9224, 2021Y9209 and 2021Y9201).