Oncogenic transformation can orchestrate immune evasion and inflammation in human mesenchymal stem cells independently of extrinsic immune-selective pressure

Alex Miranda, Juan M. Funes, Nilda Sánchez, Celia M. Limia, Mónica Mesa, Sergio A. Quezada, Rolando Pérez, Joel De León

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

4 Citas (Scopus)

Resumen

Immune escape is a hallmark of cancer, but whether it relies upon extrinsic immune-selective pressure or is inherently orchestrated by oncogenic pathways is unresolved. To address this question, we took advantage of an in vitro model of sequentially transformed human mesenchymal stem cells (hMSC). Neoplastic transformation in this model increased the natural immune-evasive properties of hMSC, both by reducing their immunogenicity and by increasing their capacity to inhibit mitogen-driven T-cell proliferation. We also found that IFNγ signaling was globally affected in transformed hMSC. As a consequence, the natural inhibitory effect of hMSC on T-cell proliferation switched from an inducible mechanism depending on IFNγ signaling and mediated by indoleamine 2,3-dioxygenase to a constitutive mechanism that relied upon IL1β involving both secreted and membrane-expressed molecules. After transformation, increased IL1β expression both sustained the immunosuppressive properties of hMSC and increased their tumorigenicity. Thus, in this model system, IL1β acted as intrinsic inflammatory mediator that exerted an autocrine influence on tumor growth by coordinately linking immune escape and tumorigenicity. Collectively, our findings show how oncogenes directly orchestrate inflammation and immune escape to drive the multistep process of cancer progression, independently of any need for immunoediting in the tumor microenvironment.

Idioma originalInglés
Páginas (desde-hasta)3032-3042
Número de páginas11
PublicaciónCancer Research
Volumen75
N.º15
DOI
EstadoPublicada - 1 ago. 2015
Publicado de forma externa

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