Science: new strategies of immunotherapy! Activation of tumor associated macrophage surface receptor cd206 enhances antitumor immune response

February 17, 2020 / Biovalley BIOON / - -- in a new study, researchers from the University of Tuskegee, the National Cancer Research Institute and the National Center for the advancement of transformation Science reported that in several types of cancer, a new immunotherapy is reprogramming immune cells, killing cancer cells and preventing tumors There is a broad prospect in growth The related research results were published in the Journal of February 12, 2020 The title of the paper is "mannose receiver (cd206) activation in tumor associated macrophases enhancements adaptive and innate antitumor immune responses" The corresponding authors of the paper are Dr Clayton Yates of Tuskegee University, Dr bolormaa baljinnyam and Dr Juan marugan of the National Center for advancing translational Sciences of the United States, and Dr Udo Rudloff of the National Cancer Institute of the United States The first authors of this paper are Jesse M Jaynes of Tuskegee University, rushikesh sable of the National Cancer Research Institute, Michael ronzetti of the National Center for advancing translational Sciences, and Wendy Bautista of the National Cancer Research Laboratory, Frederick Picture from Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aax6337 Cancer tumors evade detection and promote their own growth by manipulating the body's immune defenses The new treatment relies on small proteins called host defense peptides, which are part of our immune system's ancient defense system against bacteria, viruses and other foreign invaders Using new algorithms to detect structural similarity, the researchers found that during millions of years of evolution, a small segment of amino acids in some host defense peptides remained unchanged or changed little in different organisms They also confirmed that this method has the potential to treat other diseases as well as cancer "Cancer is essentially about our immune system - particularly the macrophages that usually surround and destroy harmful bacteria - fighting ourselves by turning them into their bodyguards," Yates explained We can confirm that these macrophages can be reprogrammed to perform their original task: to fight, not protect, harmful cancer cells " In recent years, immunotherapy using human immune system to resist diseases has made progress As a potential powerful anti-cancer tool, it has attracted many people's attention But many cancers, known as "immunologically cold cancer," do not respond to immunotherapy, including drugs called immunosuppressive checkpoint inhibitors As a result, people continue to seek new and different forms of immunotherapy to combat these often fatal diseases Dr Christopher Austin, director of the National Center for the advancement of translational Sciences, said, "immunotherapy has broad prospects and has changed the prospects of cancer treatment in an immeasurable way These findings point to a potential new way to use the immune system to fight cancer and demonstrate the value of a wide range of collaborative efforts, including preclinical studies that are essential to better understand the biological mechanisms that play a role " A few years ago, Jaynes was studying host defense peptides and their role in human infectious diseases These peptides punch holes in the bacterial cell membrane Jaynes has always seen that the small fragments of 10 to 20 amino acids in these peptides are conserved in many species For Jaynes, this may mean that they can play an important role in addition to killing cells directly Based on these observations, Jaynes and Yates speculated that some host defense peptides may have immunomodulatory functions and affect tumor associated macrophages, which are the first line of defense against infection in healthy tissues Host defense peptides attract macrophages to tissue damage sites - a process that cancer also uses to usurp macrophages to help them escape the body's immune system and promote their growth The researchers found the host defense peptide receptor cd206, which regulates this process on the surface of macrophages Cd206 may be an invasion site of macrophages in the evolution of bacteria, viruses and other invasive organisms They have constructed several synthetic peptides, including rp-182, designed to bind more strongly to specific active motifs of cd206 receptors They found that when rp-182 binds to cd206, it causes structural changes in this receptor This then activates several biological pathways and sends new chemical signals to reprogram a type of macrophage that starts killing cancer cells There are two kinds of tumor associated macrophages (TAM): M1 and M2 M1 macrophages engulf bacteria, viruses and cancer cells and cause inflammation M2 macrophages promote tissue recovery from inflammation When M2 macrophages fail to work properly, chronic inflammation can lead to diseases such as fibrosis Fibrosis is the deposition of connective tissue caused by overexpression of collagen The researchers found that rp-182 transformed M2 macrophages into M1 macrophages These reprogrammed M2 macrophages phagocytized tumor cells In the tumors treated with rp-182, M1 macrophages increased and M2 macrophages decreased Rudloff noted that rp-182 binds to the cd206 receptor and causes structural changes to the receptor, which also activates a range of other immune cells to help fight cancer "Host defense peptides existed 400 million years ago," Rudloff said We've linked evolution to immune mechanisms, from which we can make anticancer drugs Our results may have broader implications for the development of new approaches to immunotherapy " After identifying cd206 as a target for macrophages, the researchers found surprising results in animal models of different tumor types Immune cells in tumors have turned to improve tumor recognition and better monitoring to control tumors When rp-182 is used in combination with chemotherapy drugs or immunosuppressive agents in pancreatic cancer, rp-182 may play a synergistic role with drugs that are not active or have little activity in this fatal disease These results suggest that rp-182 may be used in combination with other therapies, including immunotherapy Rp-182 is particularly effective in pancreatic tumors, including those with higher levels of cd206, which are established using tumors removed during surgery Yates and his team tested rp-182 in animal models of different cancers, showing that it works not only for pancreatic cancer, but also for other cancers such as colon, breast, prostate and melanoma The application of rp-182 in diseases other than cancer through a wide range of partnerships, executive vice president of Riptide Bioscience, a California based biotechnology company Dr Lopez measured the effect of rp-182 on non cancer (such as pulmonary fibrosis) rodent models, in which pulmonary fibrosis is a fatal disease usually caused by abnormal collagen deposition in pulmonary macrophages RP-18 reduces pulmonary fibrosis and improves several clinical parameters associated with this disease, thus demonstrating the potential of rp-182 in treating diseases other than cancer Although Rudloff agreed with these preliminary results that there is hope to use rp-182 in a variety of immunotherapies, the use of rp-182 in cancer treatment is still the focus of his team's joint efforts Rudloff concluded, "for our patients, our first task is to further develop a new candidate drug as cancer therapy and put it into clinical practice There's still a long way to go " (bio Com) reference: 1 Jesse M Jaynes et al Mannose receiver (cd206) activation in more associated macrophases enhancements adaptive and native antimor immune responses Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aax6337.2 Researchers develop potential way to reprogram immune cells to fit cancer, other diseases https://medicalxpress.com/news/2020-02-potential-reprogram-immune-cells-cancer.html