Blockade of MIF-CD74 Signalling on Macrophages and Dendritic Cells Restores the Antitumour Immune Response Against Metastatic Melanoma

Página do item simplificado
dc.contributor.authorFigueiredo, Carlos Rogerio [UNIFESP]
dc.contributor.authorAzevedo, Ricardo Alexandre de [UNIFESP]
dc.contributor.authorMousdell, Sasha
dc.contributor.authorResende-Lara, Pedro T.
dc.contributor.authorIreland, Lucy
dc.contributor.authorSantos, Almudena
dc.contributor.authorGirola, Natalia [UNIFESP]
dc.contributor.authorCunha, Rodrigo L. O. R.
dc.contributor.authorSchmid, Michael C.
dc.contributor.authorPolonelli, Luciano
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.authorMielgo, Ainhoa
dc.date.accessioned2018-07-26T12:18:46Z
dc.date.available2018-07-26T12:18:46Z
dc.date.issued2018
dc.description.abstractMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment. Thus, understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that macrophages (MOs) and dendritic cells (DCs) are suppressed in metastatic melanoma and that the Ig-CDR-based peptide C36L1 is able to restore MOs and DCs' antitumorigenic and immunogenic functions and to inhibit metastatic growth in lungs. Specifically, C36L1 treatment is able to repolarize M2-like immunosuppressive MOs into M1-like antitumorigenic MOs, and increase the number of immunogenic DCs, and activated cytotoxic T cells, while reducing the number of regulatory T cells and monocytic myeloid-derived suppressor cells in metastatic lungs. Mechanistically, we find that C36L1 directly binds to the MIF receptor CD74 which is expressed on MOs and DCs, disturbing CD74 structural dynamics and inhibiting MIF signaling on these cells. Interfering with MIF-CD74 signaling on MOs and DCs leads to a decrease in the expression of immunosuppressive factors from MOs and an increase in the capacity of DCs to activate cytotoxic T cells. Our findings suggest that interfering with MIF-CD74 immunosuppressive signaling in MOs and DCs, using peptide-based immunotherapy can restore the antitumor immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the antitumor immune response in metastatic melanoma.en
dc.description.affiliationUniv Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, Sao Paulo, Brazil
dc.description.affiliationFed Univ ABC, Lab Computat Biol & Bioinformat, Santo Andre, Brazil
dc.description.affiliationEcole Normale Super, UMR 8113, LBPA, Cachan, France
dc.description.affiliationFed Univ ABC, Nat & Human Sci Ctr, Chem Biol Lab, Santo Andre, Brazil
dc.description.affiliationUniv Parma, Dept Med & Surg, Unit Biomed Biotechnol & Translat Sci, Parma, Italy
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation FAPESP
dc.description.sponsorshipSir Henry Dale research fellowship - Wellcome Trust
dc.description.sponsorshipRoyal Society
dc.description.sponsorshipIDFAPESP: 2015/23898-8
dc.description.sponsorshipIDRoyal Society: 102521/Z/13/Z
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fimmu.2018.01132
dc.identifier.citationFrontiers In Immunology. Lausanne, v. 9, p. -, 2018.
dc.identifier.doi10.3389/fimmu.2018.01132
dc.identifier.fileWOS000432830000001.pdf
dc.identifier.issn1664-3224
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/46031
dc.identifier.wosWOS:000432830000001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectmetastatic melanomaen
dc.subjectmacrophagesen
dc.subjectdendritc cellsen
dc.subjectimmune responseen
dc.subjectpeptide-based immunotherapyen
dc.subjectmacrophage migration inhibitory factoren
dc.subjectCD74en
dc.titleBlockade of MIF-CD74 Signalling on Macrophages and Dendritic Cells Restores the Antitumour Immune Response Against Metastatic Melanomaen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
WOS000432830000001.pdf
Tamanho:
5.02 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar
Coleções
EPM - Artigos