TLR9-activated B cells imprint adoptively transferred CD8+ T cells with potent tumor immunity and persistence

ABSTRACT: Here we report a new way to reverse the tolerant state of adoptively transferred CD8+ T cells against melanoma through ex vivo expansion with the TLR9 agonist CpG. CpG-generated T cells elicited potent immunity without co-administration of high dose IL-2 or vaccination, which are adjuvants classically required to effectively treat solid tumors. CpG-expanded T cells exhibited an IL-2RhighICOShighCD39low phenotype ex vivo and engrafted robustly in vivo. In culture, B cells were the only cell type essential for imprinting T cells with this phenotype and potent tumor immunity. CpG agonists targeting B cells, but not dendritic cells, generated CD8+ T cell products with remarkable antitumor properties. 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 T cells and have immediate implications for profoundly improving immunotherapy for patients.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell

SUBMITTER: Jennifer Bethard  

LAB HEAD: Chrystal Paulos PhD

PROVIDER: PXD022909 | Pride | 2022-02-22

REPOSITORIES: Pride