Zhang Xiaoyan/Jun-O Jin team found that new adjuzers can be used in tumor immunotherapy.

Cancer, as a heterogeneous disease with complex etiology, has long been considered as one of the most lethal diseases in the world.with the continuous progress of medical level, cancer treatment methods are constantly updated. Immunotherapy, as a new cancer treatment method, has attracted extensive attention of scholars, among which, dendritic cells (DC) are induced in vivo The maturation of cells (DCS) and the initiation of antigen-specific immune response is an effective way of cancer immunotherapy.however, the lack of effective immune adjuvants has become an important limiting factor in this therapeutic approach.FimH is a highly conserved protein located at the tail end of type I pili of Gram-negative bacteria such as Escherichia coli [2].studies have shown that FimH is related to the adhesion and migration of pathogenic Escherichia coli (E. coli) [3]. Systemic vaccination based on FimH can effectively prevent mucosal E. coli infection [4].it has been reported that FimH, as a ligand of Toll like receptor 4 (TLR4), can activate NK cells in mice and human by binding with TLR4 [5].however, it has not been reported that it can be used as an adjuvant in immunotherapy of cancer.on March 4, 2020, the Co-PI jun-o Jin group of Co-PI jun-o Jin team, Shanghai Public Health Clinical Center affiliated to Fudan University and Biomedical Research Institute of Fudan University, published an online paper on nature communications The adjuvant effect of E.coli adhesin FimH in cancer immunotherapy was revealed in mice and human peripheral blood cells, providing a new candidate for adjuvant in cancer immunotherapy.the FimH protein was purified by E.coli pET28a. It was proved that FimH treatment can effectively induce the activation of corresponding DCS subsets in mice and human peripheral blood cells, and play a role by enhancing Th1 and Tc1 cells.at the same time, it was proved that the activation of DCs by FimH was dependent on TLR4, but not on myeloid differentiation protein 2 (MD2).on the basis of DCS study, the researchers further proved that FimH can effectively induce the proliferation and immune response of antigen-specific T cells in mice and human peripheral blood. In addition, ova and tumor autoantigen were used in tumor mice to prove that the combination of FimH and antigen can effectively inhibit the growth of tumor cells in mice, and the antigen-specific cytokine table in vivo of mice The number of reached cells increased significantly.based on the fact that FimH is the most surface adhesin of type I fimbriae and has the natural advantage of binding with the body mucosa, the researchers evaluated the mucosal adjuvant effect of FimH. It was found that FimH can induce DCS activation through mucosal pathway, and then promote antigen-specific T cell proliferation. At the same time, the combined action of tumor antigen and FimH can significantly inhibit lung tumor growth in mice Long, increase the number of antigen-specific cells in the body.considering that the blocking of immune checkpoint and promoting the specific immune response of cancer antigen has become an immunotherapy with great application potential, in the end, the researchers explored the immunoenhancement effect of FimH combined with anti-PD-L1 in animal models, and proved that anti-PD-L1 and FimH can eliminate tumor growth and enhance the anti-tumor effect.to sum up, this project focused on the role of FimH as a novel immune adjuvant to induce the activation of DCS, promote antigen-specific immune response, and play an anti-cancer role. At the same time, the possibility of FimH as a mucosal adjuvant and joint immune checkpoint was discussed Cancer immunotherapy provides new adjuvant candidates and experimental basis.it is reported that Zhang Wei and Xu Li, research assistants of jun-o Jin research group, are the co first authors of the paper, and Professor jun-o Jin is the corresponding author of this paper. This project has been strongly supported by Professor Xu Jianqing and Professor Zhang Xiaoyan of Shanghai public health clinical center and biomedical research institute affiliated to Fudan University. Sabado, R.L., S. balan, and n. Bhardwaj, democratic cell-based immunotherapy. Cell res, 2017.27 (1): P. 74-95.2. Mydock McGrane, L.K., T.J. Hannan, and J.W. janetka, P, Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn's disease. Expert Opin Drug Discov, 2017. 12(7): p. 711-731.3. Poole, N.M., et al., Role for FimH in Extraintestinal Pathogenic Escherichia coli Invasion and Translocation through the Intestinal Epithelium. Infect Immun,2017. 85(11).4. Langermann, S., et al., Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science, 1997. 276(5312): p. 607-11.5. Mian, M.F., et al., FimH can directly activate human and murine natural killer cells via TLR4. Mol Ther, 2010. 18(7): p. 1379-88.