B cells imprint adoptively transferred CD8+ T cells with enhanced tumor immunity

Abstract

Here we report a novel strategy to reverse the tolerant state of adoptively transferred CD8+ T cells against melanoma through ex vivo expansion with the TLR9 agonist CpG. T cells generated in the presence of CpG display potent anti-tumor efficacy without in vivo co-administration of high dose IL-2 or vaccination, which are classically required for effective treatment of solid tumors using adoptive cell therapies. CD8+ T cells adopt a unique proteomic signature and are characterized by an IL-2RhighICOShighCD39low phenotype after CpG-mediated expansion. Surprisingly, we found that the presence of B cells, in the culture, was essential for imprinting CD8+ T cells with this phenotype and moreover purified B cells were sufficient to mediate the CpG-associated changes in T cells. These findings reveal a vital role for B cells in the generation of effective antitumor CD8+ T cells and have immediate implications for profoundly improving immunotherapy for patients. SUMMARY STATEMENTThe TLR9 agonist CpG allows B cells to license adoptively transferred CD8+ T cells with potent tumor immunity. These licensed T cells have a unique proteomic signature, are marked by low CD39 and high ICOS and IL-2R expression, and engraft robustly in vivo.