The
NOD-like receptor family pyrin domain-containing 3 (NLRP3)
inflammasome plays cell- and tissue-specific roles in
cancer, meaning that its activation in different
tumors or cells may play different roles in
tumor progression. We have previously described the
tumor-promoting function of
tumor-intrinsic NLRP3/IL-1β signaling in
head and neck squamous cell carcinoma (
HNSCC), but its role in immune cells remains unclear. In this study, we found that NLRP3 was highly expressed in tumor-associated macrophages (TAMs) in both mouse and human
HNSCC, and the expression of NLRP3 was positively correlated with the density of TAMs according to immunohistochemistry, immunofluorescence, and flow cytometry analyses. Importantly, the number of NLRP3high TAMs was related to worse overall survival in
HNSCC patients. Knocking out NLRP3 inhibited M2-like macrophage differentiation in vitro. Moreover, the carcinogenic effect induced by
4-nitroquinoline-1-oxide was decreased in Nlrp3-deficient mice, which had smaller
tumor sizes. Genetic depletion of NLRP3 reduced the expression of protumoral
cytokines, such as IL-1β,
IL-6,
IL-10, and CCL2, and suppressed the accumulation of TAMs and myeloid-derived suppressor cells (MDSCs) in mouse
HNSCC. Thus, activation of NLRP3 in TAMs may contribute to
tumor progression and have prognostic significance in
HNSCC.