The "helper" of anti-tumor immunotherapy has been found!

On July 8, researchers from the Cancer Center of the Sanford Burnham Prebys Institute of Medical Discovery in the United States and the Technical Comprehensive Cancer Center at the Haifa Institute of Technology in Israel found a way to turn "cold tumors" into "hot tumors." They published an article in the journal Science Translational Medicine on the mechanism of cancer immunity, confirming the therapeutic potential of epigenetic modifiers PRMT5 inhibitors to make non-reactive melanoma sensitive to immunocheckpoint therapyDOI: 10.1126/scitranslmed.aaz5683 epigenetic modifier PRMT5 (protein arginine methyl metastase 5) controls a variety of cellular processes and participates in the development and process of cancerThe researchers found that PRMT5 hides tumors from the immune system by controlling two immune signalsInhibition of PRMT5 enhances the activation of antigen presentation and innate immunity, which is a prerequisite for effective immunocheckpoint treatmentThe researchers believe the study will be a boon for those who are not responding to cancer immunotherapyIn this study, the researchers used a mouse melanoma model to combine PRMT5 inhibitors with anti-PD-1 therapy, one of the most commonly used immunocheckpoint therapy, to successfully "heat up" non-reactive "cold" tumorsNormally, mice that did not respond to PD-1 treatments lived longer after receiving PRMT5 inhibitors and had smaller tumorsThis is due to the increased ability of the immune system to attack tumorsSpecifically, the reduction in the expression of PRMT5 in melanoma cells increases the expression of NLRC5 target genes involved in antigen processing and deliveryIn contrast, the high expression of PRMT5 in cells reduces NLRC5 and inhibits the expression of its target genesIn addition, the genetic inhibition of PRMT5 increases the abundance of cytokines involved in antigen processing and presentationThese findings show that PRMT5 restricts antigen processing and presentation by regulating NLRC5 transcriptionPRMT5 regulates the production of antigens by controlling NLRC5 expression inhibits the production of cytokines And the researchers found that the decreased activity of PRMT5 in melanoma cells increased the expression of Ifnb1 and 2 chemofactors Ccl5 and Cxcl10In contrast, PRMT5 overexpression reduces the expression of more than three genes in cellsThese results show that PRMT5 can inhibit the production of interferon-beta and chemofactorsIn addition, the researchers found that PRMT5 can affect the conduction of cGAS-STING signalsInhibition of PRMT5 in melanoma cells increases the phosphorylation and dipolymerization of STING In summary, PRMT5 inhibits the activation of the cGAS/STING pathway in melanoma cells and inhibits the production of interferons and chemofactors PRMT5 regulatory cGAS/STING pathway inhibits cytokines Summary In this study, the researchers identified two cell signaling pathways suppressed by PRMT5, allowing tumors to escape immune system detection One approach is responsible for antigen presentation, and the second way controls the production of cytokines and innate immunity Together, these pathways determine the extent to which the tumor's ability to escape from the immune system As a result, their inhibition scants tumors that the immune system cannot see Based on these findings, it may be possible to help immunocheckpoint patients with tumors other than melanoma seroterins that fail to treat RELATED: PRMT5 Control of CGAS/STING and NLRC5 Pathways Defines S S S S.