TRIM22 negatively regulates MHC-II expression.

Ayano Inoue, Masashi Watanabe, Takeshi Kondo, Satoshi Hirano, Shigetsugu Hatakeyama

Biochimica et biophysica acta. Molecular cell research 2022 Oct

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The development of cancer treatment has recently achieved a remarkable breakthrough, and checkpoint blockade immunotherapy has received much attention. To enhance the therapeutic efficacy of checkpoint blockade immunotherapy, recent studies have revealed the importance of activation of CD4+ T cells via an increase in major histocompatibility complex (MHC) class II molecules in cancer cells. Here, we demonstrate that tripartite motif-containing (TRIM) 22, negatively regulates MHC-II expression. Gene knockout of TRIM22 using Cas9-sgRNAs led to an increase of MHC-II proteins, while TRIM22 overexpression remarkably decreased MHC-II proteins. mRNA levels of MHC-II and class II transactivator (CIITA), which plays an essential role in the regulation of MHC-II transcription, were not affected by TRIM22. Furthermore, TRIM22 knockout did not suppress the degradation of MHC-II protein but rather promoted it. These results suggest that TRIM22 decreases MHC-II protein levels through a combination of multiple mechanisms other than transcription or degradation. We showed that inhibition of TRIM22 can increase the amount of MHC-II expression in cancer cells, suggesting a possibility of providing the biological basis for a possible therapeutic target to potentiate checkpoint blockade immunotherapy. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Ayano Inoue, Masashi Watanabe, Takeshi Kondo, Satoshi Hirano, Shigetsugu Hatakeyama. TRIM22 negatively regulates MHC-II expression. Biochimica et biophysica acta. Molecular cell research. 2022 Oct;1869(10):119318