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IL-10 restores MHC class I expression and interferes tumor immunity in papillary thyroid cancer with concomitant Hashimotos thyroiditis

Zhong-Wu LU, Jia-Qian HUa, Li-Tao HAN, Ting-Ting ZHANG, Wen-Jun WEI, Yu-Long WANG, Yu WANG, Qing-Hai JI and Tian LIAO

Purpose: The incidence of papillary thyroid cancer (PTC) with concomitant Hashimoto’s thyroiditis (HT) is increasing. Interleukin-10 (IL-10) is a cytokine previously reported to be elevated in this condition. Evidence from multiple human malignancies showed IL-10 participated in tumor immunity and exhibited therapeutic potential. The aim of this study is to investigate whether IL-10 interferes tumor immunity in PTC with concomitant HT.

Method: Expression of IL-10 and major histocompatibility complex (MHC) class I were compared on PTC tissues with or without concomitant HT. PTC cell lines K1 and TPC-1 were stimulated with IL-10 and analyzed for MHC class I expression afterwards. T cell activation, production of Interleukin-2 (IL-2) and IFN-γ and programmed death-1 (PD-1) expression were assessed by coculture of donor peripheral blood lymphocytes (PBLs) with IL-10 pretreated PTC cells. Programmed death-ligand 1 (PD-L1) expression was measured in PTC tissues and IL-10 pretreated cells of K1 and TPC-1.

Results: Increased level of IL-10 and MHC class I were observed in PTC with concomitant HT. IL-10 stimulation increased MHC class I expression of PTC cells in vitro. Coculture of PBLs with IL-10 pretreated PTC cells enhanced T cell activation (%CD25+ of CD3+T cells) and increased IL-2 production along with decreased IFN-γ secretion and PD-1 expression. Reduced PD-L1 expression was seen in PTC+HT tissue samples and IL-10 stimulated PTC cell lines.

Conclusion: Elevated IL-10 expression in PTC with concomitant HT restores MHC class I expression and interferes tumor immunity. IL-10 may facility cancer immunotherapy in MHC class I reduced malignancies.