Curcumin enhances anti-tumor immunity in anaplastic thyroid carcinoma by elevating CD8+ T cell function and downregulating the AKT/mTORC1/STAT3/PD-L1 axis

Curcumin, a compound isolated from turmeric, has been found to have promising anti-tumor effects in various cancers, including anaplastic thyroid carcinoma (ATC). However, the molecular mechanism of curcumin in ATC remains largely unclear. CD8 +T cells could eliminate rapidly proliferating malignant cells, whereas interaction between programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) could inhibit the activation and functions of CD8 + T cells. Thus, we aimed to explore whether curcumin could inhibit ATC progression via regulating CD8 + T cells and PD-L1 expression. The protein expression of PD-L1 in ATC cells was detected by western blot assay. Additionally, a syngeneic mouse model was used to assess the effect of curcumin or/and anti-PD-1 treatment on tumorigenesis in vivo. The effect of curcumin on CD8 +T cell function was investigated by flow cytometry in vitro and in vivo. The results indicated curcumin notably suppressed ATC cell proliferation, migration and invasion and induced cell apoptosis. Additionally, curcumin could reduce PD-L1 level in ATC cells through inactivating AKT/mTORC1/STAT3 signaling. Meanwhile, curcumin obviously elevated CD8 + T cell function by elevating the number of IFN-γ producing CD8 + T cells. Furthermore, curcumin or anti-PD-L1 treatment could enhance anti-tumor immunity by increasing infiltration of CD8 + T cells in tumor tissues in vivo. As expected, compared to the single treatment, combination curcumin and anti-PD-1 treatment further elevated CD8 + T cell function in vivo, thereby potentiating anti-tumor immunity in ATC. Collectively, curcumin could enhance anti-tumor immunity in ATC by elevating CD8 + T cell function and inactivating the AKT/mTORC1/STAT3/PD-L1 axis. Our findings demonstrated a novel mechanism of the anti-tumor effects of curcumin in ATC.