Autologous graft versus myeloma: it’s not a myth
Shuai Dong, Irene M. Ghobrial
Shuai Dong, Irene M. Ghobrial
Published November 19, 2018
Citation Information: J Clin Invest. 2019;129(1):48-50. https://doi.org/10.1172/JCI125431.
View: Text | PDF
Commentary

Autologous graft versus myeloma: it’s not a myth

Abstract

Graft-versus-tumor (GVT) effects have been thought to mostly result from allogeneic transplants; however, there is a growing body of research that supports a possible autologous GVT effect. In early clinical studies, a positive correlation between lymphocyte count recovery after autologous transplantation and overall survival has been observed. However, mechanistic studies to identify the mediators of autologous GVT responses have been lacking. In this issue of the JCI, Vuckovic et al. observed a T cell–dependent autologous GVT effect in the Vk*MYC myeloma model. Moreover, the authors showed that CD8+ T cells mediate myeloma control through IFN-γ secretion, which could be further augmented with a CD137 agonist, suggesting a therapeutic approach for enhancing autologous GVT.

Authors

Shuai Dong, Irene M. Ghobrial

×

Figure 1

Autologous GVT effects are mediated by IFN-γ–expressing CD8+ T cells.

Options: View larger image (or click on image) Download as PowerPoint
Autologous GVT effects are mediated by IFN-γ–expressing CD8+ T cells. Ex...
Expansion of CD8+ T cells from autologous, myeloma-experienced BM promotes antimyeloma effects. Of the transplanted CD8+ T cell population, CD44+ cells are the most effective at killing myeloma cells, suggesting that antigen experience is critical for antitumor immunity. Th17 cells support myeloma cells via IL-17A secretion, though this effect is not the result of enhanced Th17 cell differentiation. The antimyeloma effects of CD8+ T cells are mediated by the secretion of IFN-γ, and this immunity can be enhanced by treatment with a CD137 agonist and PD-1 blockade.