PLos Biology: Effects of immune cell immersion on cancer.

, June 24, 2020 /PRNewswire/ --- -- Most traditional cancer therapies either target tumor cells themselves or indiscriminately kill any rapidly dividing cellsNew findings by researchers at the University of California, San Diego School of Medicine suggest that manipulating macrophages found in a large number of tissues around tumors is also a viable strategy for cancerthe study, published June 10, 2020 in the journal PLoS Biology, reveals for the first time the role of molecules called IRE1 alpha in influencing whether macrophages promote inflammation of tissue around cancer cellsInflammation is known to promote tumor growth and make IRE1 alpha an attractive target for future research and drug development"We know that if the tumor microenvironment is not properly regulated, when there is a mixture of pro-inflammatory and anti-inflammatory macrophages, it can impair the body's ability to fight cancer," said senior author Dr Maurizio Zanetti,and(picture:and"
IRE1 alpha is a key regulator for the abnormal response of protein folding, which is the process by which mammalian cells cope with stressTumor microenvironments put pressure on immune cells and cancer cells, isolating them from oxygen and nutrientsIRE1 alpha and unfolded protein reactions usually determine whether cells can survive under these conditionsin the new study, Zanetti and his team demonstrated for the first time that IRE1 alpha and the nonfolded protein response are also associated with abnormal immune cell function in tumor microenvironmentsThe researchers found that IRE1 alpha regulates the activation of macrophages, determining whether these rich immune cells secrete molecules that increase inflammation and produce signals that suppress the immune systemThey also found that IRE1 alpha increased PD-L1 levelsto confirm their findings in mice, Zanetti and his team looked for patterns of expression of IRE1 alpha in the Cancer Genome Map (TCGA) at the National Institutes of Health's Human Tumor Genome Information DatabaseThey found that in humanbreast and cervical cancer, the presence of macrophage IRE1 alpha indicates the expression of PD-L1 new findings in regulating PD-L1 in IRE1 alpha, because the interaction between PD-L1 on tumor cells and receptors on immune cells tells the immune system that tumor cells do not exist Checkpoint inhibitors are cancer immunotherapy that treats cancer by blocking interactions, thereby increasing the immune system's ability to fight cancer Other recent studies have shown that people's response to PD-L1 immunotherapy depends on the presence of PD-L1 on their macrophages, not on tumor cells This means that therapeutic drugs that inhibit macrophage IRE1 alpha may indirectly act as checkpoint inhibitors, allowing the immune system to better attack tumor cells on its own, Zanetti said To test this method, the team designed mice that lacked the IRE1 alpha gene in macrophages The melanoma survival rate in these IRE1 alpha-defective mice was higher than in the control group " The significance of the treatment is that we may be able to locally inhibit IRE1 alpha, thereby preventing abnormal regulation of macrophages that soak the tumor, so that the balance tends to favor the immune system rather than the tumor." There is an urgent need to develop IRE1 alpha inhibitors as related therapies " (Bio Valley Bioon.com) information source: Immune cells into the tumor s may play bigger role cancer nosa tha ethydly original source: Alyssa Batista et al, IRE1 alpha regulatessphospolar, PD-L1, and
DOI: 10.1371/journal.pbio.3000687
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