Cancer Res: Apoptosis inhibitors may promote the tolerance of certain lymphomas to a variety of therapies.

6, 2020 // -- Lymphoma is a different group of cancers in the body's immune system, which is the primary defense against autoimmune diseases, infectious diseases and malignancies, according to a recent study published in the international journal Lancer Research. Scientists at Tsukiji University have revealed risk factors and molecular mechanisms for cancer cells' primary and adaptive tolerance to cancer immunotherapy, and the findings may help develop novel therapies to treat invasive non-Hodgkin's lymphoma (NHL), which includes Burkett's lymphoma and diffuse large B-cell lymphoma.
Photo Source: One of the reasons for the failure of University of Tsukuba cancer therapy is that malignant cells can survive by avoiding apoptosis by avoiding the immune supervision of radiotherapy, chemotherapy, or endogenes, apoptosis, also known as programmed cell death, an orderly and well-designed cell suicide process that is performed primarily by regulatory proteins to react to internal pressure and external signals, and Fassum is a cellular death tolerance. the body, which binds to the ligation FasL and activates the starting factor and executioner caspases (cystic winter enzymes), which systematically degrades proteins and kills cells; 'To advance genetic modification and molecular analysis, we first simulated the development of mature B-cell lymphoma in homogenic mouse bodies, and we found that fas is necessary for the occurrence of mature B-cell lymphoma and the survival of lymphoma cells,' said
researcher Eiji Sugihara. L-induced apoptosis becomes sensitive again and prolongs survival in mice; after extending previous studies to seven human NHL cell line, the researchers confirmed that in most human cell line, the reduction in Fas expression may be restored by CD40 activation, and that this will also make about half of the cell line under study sensitive to Fas-mediated apoptosis processes.
further study, the researchers found that melanoma apoptosis protein (Livin) inhibitors may promote the tolerance of lymphoma cells to Fas-mediated apoptosis, and that BET family proteins (especially BRD4 and BND2) enhance the expression of Livin in lymphoma cells. To protect lymphoma cells from immunocytoxicity, the researchers also found that A protein-degrading IAP antagonist, BV6, could prolong the survival of mice transplanted with lymphoma cells, which previously had some tolerance to Fas-mediated apoptosis.
'In this study, we delved into the formation mechanisms of lymphoma and its patterns of resistance to immunotherapy, which induces apoptosis in cancer cells by combining the expression of CD40-mediated Fass with the use of IAP inhibitors or BET inhibitors against Livin's specific targeting effects, perhaps as a potential immunotherapy strategy to target the killing of malignant B-cell lymphoma and other refractic tumors,' the researchers said.
original source: Eiji Sugihara, Norisato Hashimoto, Satoru Osuka, et al. The resor of apoptosis protein Livin confers resistance to Fas-mediated immune cytoxicity in refractory lymphoma, Cancer Research (2020). DOI:10.1158/0008-5472.CAN-19-3993.