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• W1988434319 endingPage "e68303" @default.
• W1988434319 startingPage "e68303" @default.
• W1988434319 abstract "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 to mMSLN, a self-antigen, and deciphered the mechanism of immune responses elicited by mMSLN-VLP immunization using a pancreatic cancer (PC) mouse model. In addition to what we have found with xenogeneic human MSLN-VLP (hMSLN-VLP), mMSLN-VLP immunization was able to break the tolerance to intrinsic MSLN and mount mMSLN-specific, cytotoxic CD8(+) T cells which led to a significant reduction in tumor volume and prolonged survival in an orthotopic PC mouse model. Furthermore, CD4(+)foxp3(+) regulatory T cells (Tregs) were progressively decreased in both spleen and tumor tissues following mMSLN-VLP immunization and this was at least partly due to elevated levels of IL-6 production from activated plasmocytoid dendritic cell (pDC)-like cells following mMSLN-VLP immunization. Moreover, mMSLN-VLP treatment mainly reduced the frequency of the CD4(+)foxp3(+)ICOS(-) Treg subset. However, mMSLN-VLP induced IL-6 production also increased ICOSL expression on pDC-like cells which supported the proliferation of immunosuppressive CD4(+)foxp3(+)ICOS(+) Treg cells. This study reveals that mMSLN-VLP immunization is capable of controlling PC progression by effectively mounting an immune response against mMSLN, a tumor self-antigen, and altering the immunosuppressive tumor microenvironment via activation of pDCs-like cells and reduction in the frequency of CD4(+)foxp3(+)ICOS(-) Treg cells. However, combination therapies will likely need to be used in order to target residual CD4(+)foxp3(+)ICOS(+) Treg cells." @default.
• W1988434319 created "2016-06-24" @default.
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• W1988434319 date "2013-07-09" @default.
• W1988434319 modified "2023-10-01" @default.
• W1988434319 title "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" @default.
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• W1988434319 doi "https://doi.org/10.1371/journal.pone.0068303" @default.
• W1988434319 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3706370" @default.
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