J Cancer 2020; 11(14):4250-4260. doi:10.7150/jca.38330

Research Paper

IL-2 enhanced MHC class I expression in papillary thyroid cancer with Hashimoto's thyroiditis overcomes immune escape in vitro

Jia-Qian Hu*, Bo-Wen Lei*, Duo Wen*, Ben Ma, Ting-Ting Zhang, Zhong-Wu Lu, Wen-Jun Wei, Yu-Long Wang, Yu Wang, Duan-Shu Li, Qing-Hai Ji#✉, Tian Liao#✉

Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
* These authors contributed equally
# These authors contributed equally

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Citation:
Hu JQ, Lei BW, Wen D, Ma B, Zhang TT, Lu ZW, Wei WJ, Wang YL, Wang Y, Li DS, Ji QH, Liao T. IL-2 enhanced MHC class I expression in papillary thyroid cancer with Hashimoto's thyroiditis overcomes immune escape in vitro. J Cancer 2020; 11(14):4250-4260. doi:10.7150/jca.38330. Available from http://www.jcancer.org/v11p4250.htm

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Abstract

The impact of Hashimoto's thyroiditis (HT) on the progression of papillary thyroid cancer (PTC) is still unclear. Interleukin-2 (IL-2) is a growth factor and crucial for HT development. This study aimed at investigating the effect of IL-2 on MHC class I expression in PTC cells and immune activation with experimental treatment for PTC using PTC cell lines. We assessed the expression of IL-2, HLA class I, PD-L1, CD3, CD8 and CD16 molecules in paired PTC tissues and HLA-ABC and PD-L1 expression in IL-2 pre-treated K1, TPC-1 and BCPAP cells by immunohistochemistry, qPCR, flow cytometry and Western blotting. The effect of IL-2 on immunogenicity of PTC cells to stimulate activated human T cells was determined for the percentages of activated CD8+ T cells and their cytokine production as well as PD-1 and PD-L1 expression. Compared with non-tumor tissues, we found that IL-2 expression was up-regulated in PTC tissues, particularly in PTC+HT tissues and correlated positively with HLA-class I, CD3 and CD8 expression in PTC+HT tissues. Conversely, PD-L1 expression decreased in PTC+HT tissues. Treatment with IL-2 significantly up-regulated HLA-class I expression, but down-regulated PD-L1 expression in PTC cells. Co-culture with IL-2-pre-treated PTC cells significantly promoted the proliferation of activated CD8+ T cells and their IL-2 secretion, but decreased their PD-1 expression, accompanied by decreased PD-L1 expression in IL-2-treated PTC cells in vitro. In conclusion, IL-2 up-regulated HLA-class I expression and enhanced anti-tumor T cell immunity during the development of PTC and HT. IL-2 may be a promising immunotherapy for PTC.

Keywords: IL-2, HLA-class I molecule, papillary thyroid cancer, Hashimoto's thyroiditis, CD8+ T cell immunity