Nature Sub-Journal In-depth Analysis! How to target myelin cells to develop broad-spectrum anti-cancer therapy!

, June 29, 2020 /UPI aBiovalleyBIOON/ -- In a recent review published in the International Journal ofNature Cancer, scientists from the University of California and other institutions discussed how myelin cells are closely related to cancer therapyImmunocheckpoint blocking is very promising in cancer therapy, however, T-cell-specific checkpoint inhibitors may not be effective in treating cancer patients, and transcription factor c-Rel regulates the proactive polarization of myelin cells and the immune response of anti-
tumors50 years since the U.SNational Cancer Code declared "War on Cancer" a federal law, some of which have made significant progress in the development of targeted therapies, such as antibodies and receptor tyrosine kinase inhibitors for tumor cell receptors, or treatments based on special biomarkers, whichbiomarkers
can predict the body's effective response to cancer preparations; The field of cancer understanding and treatment is immunotherapy, where the first immunotherapy agents activate an internal immune response in cancer patients to ward off cancer advances, focusing on how to wake up depleted T-cells, and the development of T-cell checkpoint inhibitors for cancer treatment scants a significant response, although many patients, especially those whose bodies carry small or tumor-soaked T-lymphocytes, are still unable to benefit from these treatment strategiesIn the article, the researchers discussed how to inhibit tumor progression and promote theof anti-
tumors mediated by T-cell checkpoint blockers by targeting transcription factor c-Rel in immunosuppressive myelin cells, which may hopefully help researchers develop a new type of potential immunotherapyPhoto Credit: Takahashi, H., et al.
Nat Cancerdoi: 10.1038/s43018-020-0069-8
myelin cells include circulating and tissue-resident granulocytes, mononucleocytes, macrophages and dendritic cells, etc., with unique characteristics of expressing CD11b markers, and have a powerful translucent plastic potential; myelin cells in tumors are far richer than lymphocytes, and myelin cells are also rich The myelin cells circulating in the tumor host are also known as bone marrow-derived inhibitor cells (MDSCs, myeloid-reed-suppressor cells), and the researchers say c-Rel controls the polarization of myelin cells in the tumor, while c-Rel's special inhibitors can significantly inhibit tumor progression and perform a role in the development of T-immune checkpoint inhibitors These findings reveal the importance of immunosuppressive myelin cells as key regulators of the microenvironment of immune tumors c-Rel is a special transcription factor that belongs to the structure- and function-related NF-kB transcription factor-related family, which can be widely expressed in most cells and, when activated by cytokines, pathogens, or damage-related molecular pattern receptors, these transcription factors mediate the body's rapid transcription reaction, with NFNF Unlike other family members of -kB, c-Rel is expressed primarily in lymphocytes and myelin cells, and although the absence of c-Rel has not previously revealed the specific role of the factor in embryonic development, the researchers found that it plays a very important role in regulating the immune response of anti-
tumors regulated by MDSC
immune response researchers found that the growth of the and lymphoma tumors of the of the mice's congenial lineage was significantly impaired by the absence of c-Rel, and the researchers studied the loss of c-Rel in the cells of Gr1 and myelin, which were directly related to the increase in tumor growth and the increase of IFN-TNF alpha-cd8-t cells in the tumor In, the absence of c-Rel was associated with a decrease in the level of CD11b plus Gr1 plus mononucleosome s, and granulocytes in the of the blood and tumors, while the level of CD11b-F4/80-Gr1-gr1-macrophage was not affected, and the results showed that c-Rel regulates the level of MDSCs in mice, but did not affect myeloid cells in the underlying circulation of the body in healthy mice The culling of c-Rel will induce the inflammatory polarization of MDSCs, the main characteristics of which are the increase of glycoenzyme levels and the decrease of mitochondrial respiratory rate there is an urgent need for researchers to develop new therapeutic agents to inhibit the highly immunosuppressive function produced by tumor-related myelin cells, and for this reason, researchers have developed a new type of c-Rel inhibitor called R96A, which detects its effects during tumor growth in the body, and R96A significantly reduces tumor growth in wild mouse organisms (no effect on c-Rel deficiency mice), and more importantly, this therapeutic agent can block MDS The immunosuppressive effect of Cs on T cells, because T-cell checkpoint inhibitors can inhibit tumor growth that prevents T-cell depletion through a mechanism different from c-Rel inhibitors, the researchers analyzed the combination of myelin checkpoint inhibitor R96A and T-cell checkpoint inhibitor anti-PD-1 therapy, and found that this inhibitor combination may produce a powerful effect of inhibiting tumor growth compared to being used alone these findings highlight the potential for targeted signal transduction, transcription, and epigenetic genetic to control the immunosuppression of tumor , the researchers say transcription control in the immune response process may be complex, for example, and they don't know why c-Rel promotes immunosuppression in MDSCs Sex transcription, but it promotes inflammatory transcription processes in macrophages, and a detailed comparison of the expression, activation, and interaction of c-Rel in MDSCs and macrophages may help provide more clues to help develop new therapies for immunosuppression that control myelin cell-mediated Identifying therapeutic susceptibility in immunosuppressive myelin cells may be expected to enhance anti-
tumor immune strategies, and the findings could also help provide specific interactions between myelin cell signaling and transcription pathways, which may unlock and improve the efficacy of immunotherapy and thus apply it to more cancer patients, the finalists said (BioValleyBioon.com) References: Takahashi, H., Varner, J Rel-ating myeloid cells to cancer therapy Nat Cancer 1, 480-481 (2020) doi: 10.1038/s43018-020-0069-8
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