Mesothelin Virus-Like Particle Immunization Controls Pancreatic Cancer Growth through CD8+ T Cell Induction and Reduction in the Frequency of CD4+foxp3+ICOS− Regulatory T Cells

摘要: Our previous study has shown that mesothelin (MSLN) is a potential immunotherapeutic target for pancreatic cancer. Here, we further studied the immunogenicity of chimeric murine MSLN-virus-like particles (mMSLN-VLPs), their ability to break tolerance mMSLN, self-antigen, and deciphered mechanism immune responses elicited by mMSLN-VLP immunization using cancer (PC) mouse model. In addition what have found with xenogeneic human MSLN-VLP (hMSLN-VLP), was able intrinsic MSLN mount mMSLN-specific, cytotoxic CD8+ T cells which led significant reduction in tumor volume prolonged survival an orthotopic PC Furthermore, CD4+foxp3+ regulatory (Tregs) were progressively decreased both spleen tissues following this at least partly due elevated levels IL-6 production from activated plasmocytoid dendritic cell (pDC)-like immunization. Moreover, treatment mainly reduced frequency CD4+foxp3+ICOS− Treg subset. However, induced also increased ICOSL expression on pDC-like supported proliferation immunosuppressive CD4+foxp3+ICOS+ cells. This reveals capable controlling progression effectively mounting response against altering microenvironment via activation pDCs-like combination therapies will likely need be used order residual