{"doi":"10.1136/jitc-2021-003078","title":"B cells imprint adoptively transferred CD8 <sup>+</sup> T cells with enhanced tumor immunity","abstract":"Background Adoptive T cell transfer (ACT) therapy improves outcomes in patients with advanced malignancies, yet many individuals relapse due to the infusion of T cells with poor function or persistence. Toll-like receptor (TLR) agonists can invigorate antitumor T cell responses when administered directly to patients, but these responses often coincide with toxicities. We posited that TLR agonists could be repurposed ex vivo to condition T cells with remarkable potency in vivo, circumventing TLR-related toxicity. Methods In this study we investigated how tumor-specific murine CD8 + T cells and human tumor infiltrating lymphocytes (TILs) are impacted when expanded ex vivo with the TLR9 agonist CpG. Results Herein we reveal a new way to reverse the tolerant state of adoptively transferred CD8 + T cells against tumors using TLR-activated B cells. We repurposed the TLR9 agonist, CpG, commonly used in the clinic, to bolster T cell—B cell interactions during expansion for ACT. T cells expanded ex vivo from a CpG-treated culture demonstrated potent antitumor efficacy and prolonged persistence in vivo. This antitumor efficacy was accomplished without in vivo administration of TLR agonists or other adjuvants of high-dose interleukin (IL)-2 or vaccination, which are classically required for effective ACT therapy. CpG-conditioned CD8 + T cells acquired a unique proteomic signature hallmarked by an IL-2Rα high ICOS high CD39 low phenotype and an altered metabolic profile, all reliant on B cells transiently present in the culture. Likewise, human TILs benefitted from expansion with CpG ex vivo, as they also possessed the IL-2Rα high ICOS high CD39 low phenotype. CpG fostered the expansion of potent CD8 + T cells with the signature phenotype and antitumor ability via empowering a direct B–T cell interaction. Isolated B cells also imparted T cells with the CpG-associated phenotype and improved tumor immunity without the aid of additional antigen-presenting cells or other immune cells in the culture. Conclusions Our results demonstrate a novel way to use TLR agonists to improve immunotherapy and reveal a vital role for B cells in the generation of potent CD8 + T cell-based therapies. Our findings have immediate implications in the clinical treatment of advanced solid tumors.","journal":"Journal for ImmunoTherapy of Cancer","year":2022,"id":259764,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314034,"name":"Hannah M. Knochelmann","orcid":"0000-0003-0644-123X","position":1,"is_corresponding":false},{"id":314036,"name":"Megan M. Wyatt","orcid":"0000-0003-1316-260X","position":2,"is_corresponding":false},{"id":314033,"name":"Guillermo O. Rangel Rivera","orcid":"0000-0001-9364-6385","position":3,"is_corresponding":false},{"id":631314,"name":"Amalia M Rivera-Reyes","orcid":null,"position":4,"is_corresponding":false},{"id":314031,"name":"Connor J. Dwyer","orcid":"0000-0002-2306-0570","position":5,"is_corresponding":false},{"id":354296,"name":"Michael B. Ware","orcid":"0000-0002-6139-1952","position":6,"is_corresponding":false},{"id":912893,"name":"Anna C Cole","orcid":null,"position":7,"is_corresponding":false},{"id":314040,"name":"David M. Neskey","orcid":"0000-0003-2026-2406","position":8,"is_corresponding":false},{"id":314037,"name":"Mark P. Rubinstein","orcid":"0000-0003-4748-0286","position":9,"is_corresponding":false},{"id":317575,"name":"Bei Liu","orcid":"0000-0002-5198-0796","position":10,"is_corresponding":false},{"id":314039,"name":"Jessica E. Thaxton","orcid":"0000-0003-1759-5576","position":11,"is_corresponding":false},{"id":454361,"name":"Eric Bartee","orcid":"0000-0003-1793-446X","position":12,"is_corresponding":false},{"id":314041,"name":"Chrystal M. Paulos","orcid":"0000-0002-0784-2601","position":13,"is_corresponding":false},{"id":314035,"name":"Aubrey S. Smith","orcid":"0000-0003-3693-4262","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T00:25:58.993402Z","pmid":"35017148","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}