The inflammatory status of soluble microenvironment influences the capacity of melanoma cells to control t-cell responses

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MetadadosDescriçãoIdioma
Autor(es): dc.creatorBogéa, Gabriela Muller Reche-
Autor(es): dc.creatorCarvalho, Amandda Évelin Silva-
Autor(es): dc.creatorBraga, Luma Dayane de Carvalho Filiú-
Autor(es): dc.creatorNeves, Francisco de Assis Rocha-
Autor(es): dc.creatorAraujo, Felipe Saldanha de-
Data de aceite: dc.date.accessioned2022-08-15T13:38:18Z-
Data de disponibilização: dc.date.available2022-08-15T13:38:18Z-
Data de envio: dc.date.issued2022-05-09-
Data de envio: dc.date.issued2022-05-09-
Data de envio: dc.date.issued2021-
Fonte completa do material: dc.identifierhttps://repositorio.unb.br/handle/10482/43672-
Fonte completa do material: dc.identifierhttps://doi.org/10.3389/fonc.2022.858425-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/713465-
Descrição: dc.descriptionThe development of immunotherapeutic approaches for the treatment of melanoma requires a better understanding of immunoescape mechanisms of tumor cells and how they interact with other tumor-resident cell types. Here, we evaluated how the conditioned media of resting (rCM) and immune-activated PBMCs (iCM) influence the ability of a metastatic melanoma cell line (MeWo) to control T-cells function. MeWo cells were expanded in RPMI, rCM, or iCM and the secretome generated after cell expansion was identified as MeSec (RPMI), niSec (non-inflammatory), or iSec (inflammatory secretome), respectively. Then, the immunomodulatory potential of such secretomes was tested in PHA-activated PBMCs. iCM induced higher levels of IFN-γ and IL-10 in treated melanoma cells compared to rCM, as well as higher IDO and PD-L1 expression. The iSec was able to inhibit T-cell activation and proliferation. Interestingly, PBMCs treated with iSec presented a reduced expression of the regulators of Th1 and Th2 responses T-BET and GATA-3, as well as low expression of IFN-γ, and co-stimulatory molecules TIM-3 and LAG-3. Importantly, our findings show that melanoma may benefit from an inflammatory microenvironment to enhance its ability to control the T-cell response. Interestingly, such an immunomodulatory effect involves the inhibition of the checkpoint molecules LAG-3 and TIM-3, which are currently investigated as important therapeutic targets for melanoma treatment. Further studies are needed to better understand how checkpoint molecules are modulated by paracrine and cell contact-dependent interaction between melanoma and immune cells. Such advances are fundamental for the development of new therapeutic approaches focused on melanoma immunotherapy.-
Formato: dc.formatapplication/pdf-
Publicador: dc.publisherFrontiers-
Direitos: dc.rightsAcesso Aberto-
Direitos: dc.rights(CC BY)-
Palavras-chave: dc.subjectMelanoma-
Palavras-chave: dc.subjectCélulas T-
Palavras-chave: dc.subjectResposta imunológica-
Palavras-chave: dc.subjectSecretoma-
Título: dc.titleThe inflammatory status of soluble microenvironment influences the capacity of melanoma cells to control t-cell responses-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional – UNB

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