Chinese scientists: Gut bacteria can enter tumors, enhance CD47 antibody antibody anti-cancer efficacy

A new study published March 6 in the journal Of Experimental Medicine revealed that gut bacteria can penetrate tumor cells, improving the effectiveness of experimental immunotherapy that targets CD47using a mouse model of malignant tumors, a team of scientists led by Professor Fu Yangxin of the University of Texas Southwestern Medical Center and Professor Ralph RWeichselbaum of the University of Chicago found that the accumulation of the gut microbe Bifidobacteria in the tumor makes tumors that do not respond to CD47 antibodies respond to CD47 antibodiesBifidobacteria from the gastrointestinal tract to the tumor, by activating the immune signaling pathway, the response of mice to immunotherapy CD47 antibodies was enhanced(Source: Journal of App Cono Medicine)CD47 is a protein widely expressed on the surface of normal cells that releases a "don't eat me" signal by binding to SIRP alpha on the surface of macrophages, protecting healthy cells from macrophagesUnfortunately, cancer cells have also learned this mechanism: over-expressing CD47 on the surface, causing macrophages to treat them as "normal cells" and thus avoid being "eaten"Based on these findings, the scientists began investigating the anti-cancer effects of CD47 blocking therapy (anti-CD47 therapy)Although several CD47 antibodies and targeted CD47 small molecule drugs have entered clinical trials, the pre-trial results in mice were "mixed" and only some mice responded to CD47 blocking therapyin this new study, scientists are curious about how the gut flora regulates anti-CD47 therapy, given that there is evidence that gut microbes known as the "second genome" of humans can influence the host's response to cancer immunotherapy, such as PD-1 antibodiesBifidobacteria administration fully restored the anti-tumor efficacy of anti-CD47 immunotherapy in non-responders (Source: Journal of Trial Medicine)they found that mice that normally responded to anti-CD47 therapy were no longer able to respond to anti-CD47 therapy if they were killed with antibiotic "cocktail therapy" for their gut bacteriaIn contrast, the treatment became effective in mice that had been given Bifidobacteria, a common bacteria in healthy mice and the human gastrointestinal tract, when they were given bifidobacteria, a common bacteria in healthy mice and human segastrointestinal tractsfibrous sinoma promotes CD47-based immunotherapy through STING signals (Source: Journal of The Journal of Free Of The Core)mechanisms have shown that Bifidobacteria migrate to tumor stoma cells or microenvironments, where STING is activated in the body's innate immune system the genes) pathway, which further leads to the production of immune signaling molecules (such as type I interferon) and the activation of immune cells (activates dendritic cells, which cross-transmit tumor antigens to T cells), thereby creating synergistic antitumor effects with CD47 antibodiesresearchers also found that mice genetically modified to activate type I interferon were unable to respond to the "intestinal bacteria-CD47 antibody" combination therapy, as were mice that were unable to initiate the STING pathway, suggesting that the STING signaling pathway was necessary for this combination therapyconcluded, Professor Fu said the results suggest that specific members of the gut microbiome are expected to enhance the anti-tumor efficacy of anti-CD47 therapy by planting in tumors In addition, it is likely that more than one gut microbe can enhance anti-tumor immunity in a similar way The administration of a particular strain or its engineering "offspring" may be a new effective strategy for regulating a variety of anti-tumor immunotherapy therapies Therefore, they will continue their research source: Professor Fu Yangxin, of the University of Texas Southwestern Medical Center, is one of the leading scientists in the field of tumor immunity and has published a number of important and innovative research papers in the journals Science, Nature, Nature Immunology and others in an interview with Pharmaceutical Rubik's Cube Pro, said the team began working on CD47 in 2010, when he was interested in tumor-killing antibodies In addition to the new advances published in the journal JEM, the team has made other important findings related to CD47 in recent years , a 2015 paper published in the journal Nature Medicine was the first to reveal that the therapeutic effect of CD47 blocking relies on the cross-initiation of dendritic cells, rather than macrophages, to respond to T-cells In Mice with T-cell defects, CD47 antibodies had no therapeutic effect In addition, studies have shown that CD47 blocking the anti-tumor effect requires the expression of the innate immunoprotein STING 2017 study published in the journal Immunity further suggests that while macrophages can ingest tumor DNA more effectively, the increased DNA sensing by blocking CD47-SIRP alpha interactions occurs first in dendritic cells rather than macrophages (knowledge supplement: inhibition of cytoplasmic DNA sensing is a strategy used by tumor cells for immune escape) On the mechanism, CD47 blocks the activation of NADPH oxidase NOX2 in dendritic cells, thereby inhibiting phage acidification and reducing the degradation of tumor mitochondrial DNA (mtDNA) in dendritic cells Tumor mtDNA is then identified by cGAS (cyclic-GMP-AMPsynthase) in dendritic cytoplasm, which promotes the production of type I interferon and anti-tumor adaptive immunity 2018, the team also confirmed that CD47 and PD-L1 expressed by tumor cells work together to suppress innate and adaptive induction to evade immune control Compared with monoantigens, both PD-L1-SIRP alpha bispecific antibodies were targeted to block CD47 and PD-L1 significantly enhance tumor targeting and therapeutic effects The results were published in the journal Cell Reports Professor Fu Yangxin, who has been in the CD47 field for 10 years, who has been in the believes that anti-CD47 therapy needs to be improved to better understand the mechanisms Because CD47 is also expressed in normal cells, including red blood cells, it is important to develop candidate molecules that selectively block the CD47-SIRP alpha pathway in tumor cells As for the prospect of anti-CD47 therapy, Professor Fu Summing up a sentence: Good for liquid tumor but not easy for solid tumor yet related papers Journal of Experiment Medicine (2020) 2) Bertrand Routy et al Gut microbiome influences efficacy of PD-1-generation aegypti sanest epithelial tumors Science (2018) Gopalakrishnan et al Gut microbiome modulates response to anti-PD-1immunotherapy in melanoma patients Science (2018) Vyara Matson et al The commensal microbiomeis associated with anti-PD-1 efficacy inmeta melanoma patients Science (2018) aylet Sivan et al Commensal Bifidobacterium promotes antitumor immunity and promotes anti-PD-L1 feacy Science (2015) Takeshi Tanoue et al Aged commensal elicits CD8 T cells and anti-cancer immunity Nature (2019) 7) Xiaojuan Liu et al CD47 blockade triggers T cell-mediated destruction of immun tumorogenics Nature Medicine (2015) Meng Michelle Xu et al Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming Signal Snr Alpha Signaling Immunity (2017) Cell Reports (2018) Mingye Feng et al Phagocytosis checkpoints as new targets for cancer immunotherapy Nature Reviews Cancer (2019) references: 1- can't be cancer edg-gu bacteria? (source: University of Texas Southwestern Medical Center) 2?gut bacteria can can find sapos and aid cancer therapy, study suggests (source: Rockefeller University Press) 3? I know immunologist Professor Fu Yangxin (source: Us Medicine Source) 4 s CD47 and SIRP alpha scarcityofed in the squamous cell