Thursday, October 25, 2012
Figure 1. Resistance to adoptive T cell therapy via dedifferentiation. As reported by
Landsberg et al., melanoma cells can undergo inflammation-induced
dedifferentiation. The process is a potential acquired resistance mechanism
against adoptive cell transfer therapies.
Melanoma cells exposed to the proinflammatory cytokine tumor necrosis factor-α
(TNF-a) undergo reversible dedifferentiation.
Cells with the dedifferentiated phenotype show downregulated expression of
Adoptive cell transfer therapies for melanoma can involve the infusion of T
cells engineered to express antigen receptors that recognize melanocytic
antigens. The dedifferentiation mechanism could contribute to resistance
against such therapies.
cells recognize antigens expressed by the melanoma cells and trigger an immune
response (II[a]). However, TNF-a released
by these T cells during the immune response also can trigger the dedifferentiation
process (II[b]). The infused T cells are unable to recognize
dedifferentiated melanoma cells. Over time, these dedifferentiated cells regrow
and become the dominant cellular phenotype in the tumor (II[c]).