TRIM22 negatively regulates MHC-II expression

Biochim Biophys Acta Mol Cell Res. 2022 Oct;1869(10):119318. doi: 10.1016/j.bbamcr.2022.119318. Epub 2022 Jun 28.


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.

Keywords: Checkpoint blockade immunotherapy; IFN-γ; MHC-II; TRIM22; Ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Histocompatibility Antigens Class II / genetics
  • Immune Checkpoint Inhibitors*
  • Interferon-gamma* / pharmacology
  • RNA, Messenger


  • Histocompatibility Antigens Class II
  • Immune Checkpoint Inhibitors
  • RNA, Messenger
  • Interferon-gamma