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Cell Rep Med ; 2(12): 100473, 2021 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-35028614

RESUMEN

Despite its role in cancer surveillance, adoptive immunotherapy using γδ T cells has achieved limited efficacy. To enhance trafficking to bone marrow, circulating Vγ9Vδ2 T cells are expanded in serum-free medium containing TGF-ß1 and IL-2 (γδ[T2] cells) or medium containing IL-2 alone (γδ[2] cells, as the control). Unexpectedly, the yield and viability of γδ[T2] cells are also increased by TGF-ß1, when compared to γδ[2] controls. γδ[T2] cells are less differentiated and yet display increased cytolytic activity, cytokine release, and antitumor activity in several leukemic and solid tumor models. Efficacy is further enhanced by cancer cell sensitization using aminobisphosphonates or Ara-C. A number of contributory effects of TGF-ß are described, including prostaglandin E2 receptor downmodulation, TGF-ß insensitivity, and upregulated integrin activity. Biological relevance is supported by the identification of a favorable γδ[T2] signature in acute myeloid leukemia (AML). Given their enhanced therapeutic activity and compatibility with allogeneic use, γδ[T2] cells warrant evaluation in cancer immunotherapy.


Asunto(s)
Inmunoterapia Adoptiva , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Células de la Médula Ósea/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Medio de Cultivo Libre de Suero/farmacología , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Humanos , Inmunofenotipificación , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Activación de Linfocitos , Ratones SCID , Pronóstico
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