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Promotion on NLRC5 upregulating MHC-I expression by IFN-γ in MHC-I–deficient breast cancer cells

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Abstract

Breast cancer is the most dominant cancer in women and the second most frequent cancer in the general population worldwide. NLRC5 critically transactivates MHC class I (classically HLA-ABC in human) which is crucial for cancer immunosurveillance. But the expressional and functional impairments of NLRC5 have been found in many cancers as a major mechanism of immune evasion. Promotion of NLRC5 with the enhancement of MHC class I contributes to cancer immunotherapy and counteraction against cancer immune evasion. In many cancers, IFN-γ promotes the expression of MHC class I involving NLRC5; however, it is unclear in breast cancer cells. In this study, qRT-PCR, western blot, and flow cytometry were used to detect the mRNAs and proteins of NLRC5, β2m, and HLA-ABC in MHC class I–deficient human SKBR3 breast cancer cells after IFN-γ treatment. It was shown that the relative levels of NLRC5 mRNA, β2m mRNA, and HLA-ABC α heavy chain mRNA, in concentrations of 50 U/ml and 100 U/ml IFN-γ groups, were statistically increased (p < 0.05) with dose dependent tendency compared with the control group. The protein levels of NLRC5 and β2m in concentrations of 50 U/ml and 100 U/ml IFN-γ groups, HLA-ABC (positive rates) in different concentrations of IFN-γ groups, were statistically increased (p < 0.05), with dose dependent tendency for NLRC5 and HLA-ABC, compared with the control group. Promotion of NLRC5 by IFN-γ with upregulation of MHC class I (HLA-ABC) in SKBR3 breast cancer cells, suggesting the contribution to counteracting cancer evasion from immunosurveillance and benefiting cancer immunotherapy.

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  1. Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei, China

    Ming-Zhen Zhao, Yu Sun, Xiao-Feng Jiang, Li Liu, Li Liu & Li-Xin Sun

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Zhao, MZ., Sun, Y., Jiang, XF. et al. Promotion on NLRC5 upregulating MHC-I expression by IFN-γ in MHC-I–deficient breast cancer cells. Immunol Res 67, 497–504 (2019). https://doi.org/10.1007/s12026-019-09111-w

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