ABSTRACTThe association betweenCandida albicans(C. albicans) and oral cancer (OC) has been noticed for a long time, but the mechanisms forC. albicanspromoting OC are rarely explored. In this study, we determined thatC. albicansinfection promoted OC incidence in a 4-nitroquinoline 1-oxide (4NQO)-induced mouse tongue carcinogenesis model as well as promoted OC progression in a tongue tumor-bearing mouse model (C3H/HeN-SCC VII). We then demonstrated that tumor-associated macrophage (TAMs) infiltration was elevated duringC. albicansinfection. Meanwhile, the attracted TAMs polarized into M2-like macrophages with high expression of programmed death ligand 1 (PD-L1) and galectin-9 (GAL-9). Further analysis suggested that the interleukin (IL)-17A/IL-17RA pathway activated in OC cells was a contributor to the excessive TAMs infiltration inC. albicans-infected mice. Thus, we constructed IL-17A neutralization and macrophage depletion experiments in C3H/HeN-SCC VII mice to explore the role of IL-17A/IL-17RA and TAMs in OC development caused byC. albicansinfection. The results showed that both IL-17A neutralization and macrophage depletion tended to reduce the TAMs number and tumor size in mice withC. albicansinfection. Collectively, our finding revealed thatC. albicanspromoted OC development via the IL-17A/IL-17RA-macrophage axis, opening perspectives for revealingC. albicans-tumor immune microenvironment links.