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Blocking drug-induced autophagy with chloroquine in HCT-116 colon cancer cells enhances DC maturation and T cell responses induced by tumor cell lysate

dc.contributor.authorZamame Ramirez, Jofer Andree [UNESP]
dc.contributor.authorRomagnoli, Graziela Gorete [UNESP]
dc.contributor.authorFalasco, Bianca Francisco [UNESP]
dc.contributor.authorGorgulho, Carolina Mendonça [UNESP]
dc.contributor.authorSanzochi Fogolin, Carla [UNESP]
dc.contributor.authordos Santos, Daniela Carvalho [UNESP]
dc.contributor.authorJunior, João Pessoa Araújo [UNESP]
dc.contributor.authorLotze, Michael Thomas
dc.contributor.authorUreshino, Rodrigo Portes
dc.contributor.authorKaneno, Ramon [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversity of Pittsburgh
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2020-12-12T02:01:53Z
dc.date.available2020-12-12T02:01:53Z
dc.date.issued2020-07-01
dc.description.abstractAutophagy is an important mechanism for tumor escape, allowing tumor cells to recover from the damage induced by chemotherapy, radiation therapy, and immunotherapy and contributing to the development of resistance. The pharmacological inhibition of autophagy contributes to increase the efficacy of antineoplastic agents. Exposing tumor cells to low concentrations of select autophagy-inducing antineoplastic agents increases their immunogenicity and enhances their ability to stimulate dendritic cell (DC) maturation. We tested whether the application of an autophagy-inhibiting agent, chloroquine (CQ), in combination with low concentrations of 5-fluorouracil (5-FU) increases the ability of tumor cells to induce DC maturation. DCs sensitized with the lysate of HCT-116 cells previously exposed to such a combination enhanced the DC maturation/activation ability. These matured DCs also increased the allogeneic responsiveness of both CD4+ and CD8+ T cells, which showed a greater proliferative response than those from DCs sensitized with control lysates. The T cells expanded in such cocultures were CD69+ and PD-1- and produced higher levels of IFN-γ and lower levels of IL-10, consistent with the preferential activation of Th1 cells. Cocultures of autologous DCs and lymphocytes improved the generation of cytotoxic T lymphocytes, as assessed by the expression of CD107a, perforin, and granzyme B. The drug combination increased the expression of genes related to the CEACAM family (BECN1, ATGs, MAPLC3B, ULK1, SQSTM1) and tumor suppressors (PCBP1). Furthermore, the decreased expression of genes related to metastasis and tumor progression (BNIP3, BNIP3L, FOSL2, HES1, LAMB3, LOXL2, NDRG1, P4HA1, PIK3R2) was noted. The combination of 5-FU and CQ increases the ability of tumor cells to drive DC maturation and enhances the ability of DCs to stimulate T cell responses.en
dc.description.affiliationSão Paulo State University – UNESP Department of Chemical and Biological Sciences Institute of Biosciences of Botucatu
dc.description.affiliationSão Paulo State University – UNESP Department of Pathology School of Medicine of Botucatu
dc.description.affiliationSão Paulo State University – UNESP Center for Electron Microscopy Institute of Biosciences of Botucatu
dc.description.affiliationDepartment of Immunology University of Pittsburgh
dc.description.affiliationFederal University of São Paulo – UNIFESP Department of Biological Sciences
dc.description.affiliationUnespSão Paulo State University – UNESP Department of Chemical and Biological Sciences Institute of Biosciences of Botucatu
dc.description.affiliationUnespSão Paulo State University – UNESP Department of Pathology School of Medicine of Botucatu
dc.description.affiliationUnespSão Paulo State University – UNESP Center for Electron Microscopy Institute of Biosciences of Botucatu
dc.description.sponsorshipHigher College of Technology
dc.description.sponsorshipIdHigher College of Technology: CEACAM 5
dc.identifierhttp://dx.doi.org/10.1016/j.intimp.2020.106495
dc.identifier.citationInternational Immunopharmacology, v. 84.
dc.identifier.doi10.1016/j.intimp.2020.106495
dc.identifier.issn1878-1705
dc.identifier.issn1567-5769
dc.identifier.lattes8845835550637809
dc.identifier.orcid0000-0002-4292-3298
dc.identifier.scopus2-s2.0-85083047237
dc.identifier.urihttp://hdl.handle.net/11449/200260
dc.language.isoeng
dc.relation.ispartofInternational Immunopharmacology
dc.sourceScopus
dc.subjectAutophagy
dc.subjectCancer
dc.subjectChemotherapy
dc.subjectColorectal
dc.subjectCytotoxic T cells
dc.subjectDendritic cells
dc.titleBlocking drug-induced autophagy with chloroquine in HCT-116 colon cancer cells enhances DC maturation and T cell responses induced by tumor cell lysateen
dc.typeArtigo
dspace.entity.typePublication
unesp.author.lattes8845835550637809[10]
unesp.author.orcid0000-0002-4292-3298[10]
unesp.campusUniversidade Estadual Paulista (UNESP), Faculdade de Medicina, Botucatupt
unesp.departmentPatologia - FMBpt

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