Titre:	The inflammatory status of soluble microenvironment influences the capacity of melanoma cells to control t-cell responses
Auteur(s):	Bogéa, Gabriela Muller Reche Carvalho, Amandda Évelin Silva de Braga, Luma Dayane de Carvalho Filiú Neves, Francisco de Assis Rocha Araujo, Felipe Saldanha de
Assunto::	Melanoma Células T Resposta imunológica Secretoma
Date de publication:	2022
Editeur:	Frontiers
Référence bibliographique:	BOGÉA, Gabriela Muller Reche et al. The inflammatory status of soluble microenvironment influences the capacity of melanoma cells to control t-cell responses. Frontiers in Oncology, v. 12, 858425, 2022. DOI: https://doi.org/10.3389/fonc.2022.858425. Disponível em: https://www.frontiersin.org/articles/10.3389/fonc.2022.858425/full. Acesso em: 9 maio 2022.
Abstract:	The 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.
Licença::	(CC BY)
DOI:	https://doi.org/10.3389/fonc.2022.858425
Collection(s) :	Artigos publicados em periódicos e afins

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