Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9

Abstract

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8 + T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8 + T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Research progress of immunotherapy against anaplastic thyroid cancer

“…By producing IL-6, TNF-α, and CXC chemokine ligand 8 (CXCL8)/IL-8, MCs aid epithelial–mesenchymal transition in ATC cells ( 28 ). Galectin-9 aids MC support of ATC cell adhesion, angiogenesis, metastasis, and tumor immune escape ( 29 ). Most of the body’s professional antigen-presenting cells are termed DCs, yet the amount of DCs in ATC is much lower than that of other thyroid cancers ( 30 , 31 ).…”