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

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

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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 https://www.jcancer.org/v11p4250.htm

File import instruction in vitro^~^2020^~^11^~^14^~^4250^~^4260^~^10.7150/jca.38330^~^https://www.jcancer.org/v11p4250.htm'>


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