{"doi":"10.3389/fimmu.2023.1295218","title":"Antigen-presenting B cells promote TCF-1+ PD1- stem-like CD8+ T-cell proliferation in glioblastoma","abstract":"Understanding the spatial relationship and functional interaction of immune cells in glioblastoma (GBM) is critical for developing new therapeutics that overcome the highly immunosuppressive tumor microenvironment. Our study showed that B and T cells form clusters within the GBM microenvironment within a 15-μm radius, suggesting that B and T cells could form immune synapses within the GBM. However, GBM-infiltrating B cells suppress the activation of CD8 + T cells. To overcome this immunosuppression, we leveraged B-cell functions by activating them with CD40 agonism, IFNγ, and BAFF to generate a potent antigen-presenting B cells named B Vax . B Vax had improved antigen cross-presentation potential compared to naïve B cells and were primed to use the IL15-IL15Ra mechanism to enhance T cell activation. Compared to naïve B cells, B Vax could improve CD8 T cell activation and proliferation. Compared to dendritic cells (DCs), which are the current gold standard professional antigen-presenting cell, B Vax promoted highly proliferative T cells in-vitro that had a stem-like memory T cell phenotype characterized by CD62L + CD44 - expression, high TCF-1 expression, and low PD-1 and granzyme B expression. Adoptive transfer of B Vax -activated CD8 + T cells into tumor-bearing brains led to T cell reactivation with higher TCF-1 expression and elevated granzyme B production compared to DC-activated CD8 + T cells. Adoptive transfer of B Vax into an irradiated immunocompetent tumor-bearing host promoted more CD8 + T cell proliferation than adoptive transfer of DCs. Moreover, highly proliferative CD8 + T cells in the B Vax group had less PD-1 expression than those highly proliferative CD8 + T cells in the DC group. The findings of this study suggest that B Vax and DC could generate distinctive CD8 + T cells, which potentially serve multiple purposes in cellular vaccine development.","journal":"Frontiers in Immunology","year":2024,"id":434597,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":568159,"name":"Hanxiao Wan","orcid":null,"position":1,"is_corresponding":false},{"id":1026917,"name":"Joshua L. 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