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

Smith, A. S.; Knochelmann, H. M.; Wyatt, M. M.; Rangel Rivera, G. O.; Rivera-Reyes, A. M.; Dwyer, C. J.; Neskey, D. M.; Rubinstein, M. P.; Liu, B.; Thaxton, J. E.; Bartee, E.; Paulos, C. M.

doi:10.1101/2021.03.16.435714

bioRxiv · 10.1101/2021.03.16.435714

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

Smith, A. S.·Knochelmann, H. M.·Wyatt, M. M.·Rangel Rivera, G. O.·Rivera-Reyes, A. M.·Dwyer, C. J.·Neskey, D. M.·Rubinstein, M. P.·Liu, B.·Thaxton, J. E.·Bartee, E.·Paulos, C. M.

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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.

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Smith, A. S., Knochelmann, H. M., Wyatt, M. M., Rangel Rivera, G. O., Rivera-Reyes, A. M., Dwyer, C. J., Neskey, D. M., Rubinstein, M. P., Liu, B., Thaxton, J. E., Bartee, E., Paulos, C. M.. 2021-03-17. B cells imprint adoptively transferred CD8+ T cells with enhanced tumor immunity. https://doi.org/10.1101/2021.03.16.435714

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