Data from Adoptive Cell Therapy for Lymphoma with CD4 T Cells Depleted of CD137-Expressing Regulatory T Cells

Adoptive immunotherapy with antitumor T cells is a promising novel approach for the treatment of cancer. However, T-cell therapy may be limited by the cotransfer of regulatory T cells (T_reg). Here, we explored this hypothesis by using 2 cell surface markers, CD44 and CD137, to isolate antitumor CD4 T cells while excluding T_regs. In a murine model of B-cell lymphoma, only CD137^negCD44^hi CD4 T cells infiltrated tumor sites and provided protection. Conversely, the population of CD137^posCD44hi CD4 T cells consisted primarily of activated T_regs. Notably, this CD137^pos T_reg population persisted following adoptive transfer and maintained expression of FoxP3 as well as CD137. Moreover, in vitro these CD137^pos cells suppressed the proliferation of effector cells in a contact-dependent manner, and in vivo adding the CD137^posCD44^hi CD4 cells to CD137^negCD44^hi CD4 cells suppressed the antitumor immune response. Thus, CD137 expression on CD4 T cells defined a population of activated T_regs that greatly limited antitumor immune responses. Consistent with observations in the murine model, human lymphoma biopsies also contained a population of CD137^pos CD4 T cells that were predominantly CD25^posFoxP3^pos T_regs. In conclusion, our findings identify 2 surface markers that can be used to facilitate the enrichment of antitumor CD4 T cells while depleting an inhibitory T_reg population. Cancer Res; 72(5); 1239–47. ©2012 AACR.