{"doi":"10.4049/jimmunol.2000007","title":"Adoptive T Cell Therapy with IL-12–Preconditioned Low-Avidity T Cells Prevents Exhaustion and Results in Enhanced T Cell Activation, Enhanced Tumor Clearance, and Decreased Risk for Autoimmunity","abstract":"T cell expansion and melanoma regression; however, adverse side effects, including autoimmunity, can occur. This may be due to transfer of high-avidity self-specific T cells. In this study, we compared mouse low- and high-avidity T cells targeting the tumor Ag tyrosinase-related protein 2 (TRP2). Not surprisingly, high-avidity T cells provide superior tumor control, yet low-avidity T cells can promote tumor regression. The addition of IL-12 during in vitro expansion boosts low-avidity T cell responsiveness, tumor regression, and prevents T cell exhaustion. In this study, we demonstrate that IL-12-primed T cells are resistant to PD-1/PD-L1-mediated suppression and retain effector function. Importantly, IL-12 preconditioning prevented exhaustion as LAG-3, PD-1, and TOX were decreased while simultaneously increasing KLRG1. Using intravital imaging, we also determined that high-avidity T cells have sustained contacts with intratumoral dendritic cells and tumor targets compared with low-avidity T cells. However, with Ag overexpression, this defect is overcome, and low-avidity T cells control tumor growth. Taken together, these data illustrate that low-avidity T cells can be therapeutically beneficial if cocultured with IL-12 cytokine during in vitro expansion and highly effective in vivo if Ag is not limiting. Clinically, low-avidity T cells provide a safer alternative to high-avidity, TCR-engineered T cells, as IL-12-primed, low-avidity T cells cause less autoimmune vitiligo.","journal":"The Journal of Immunology","year":2020,"id":96015,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":266265,"name":"Jason S. Mitchell","orcid":"0000-0002-4669-9481","position":1,"is_corresponding":false},{"id":476615,"name":"Tijana Martinov","orcid":"0000-0002-6027-3380","position":2,"is_corresponding":false},{"id":476616,"name":"Brandon J. Burbach","orcid":"0000-0003-0922-7722","position":3,"is_corresponding":false},{"id":266260,"name":"Lalit K. Beura","orcid":"0000-0002-8597-3949","position":4,"is_corresponding":false},{"id":476617,"name":"Joseph Wilson","orcid":"0000-0001-6120-8962","position":5,"is_corresponding":false},{"id":477899,"name":"Alexander J. Dwyer","orcid":null,"position":6,"is_corresponding":false},{"id":477900,"name":"Lovejot M. Singh","orcid":null,"position":7,"is_corresponding":false},{"id":477901,"name":"Matthew F. Mescher","orcid":null,"position":8,"is_corresponding":false},{"id":247528,"name":"Brian T. Fife","orcid":"0000-0001-9826-5637","position":9,"is_corresponding":false},{"id":247527,"name":"Christopher Tucker","orcid":"0000-0002-5376-240X","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T22:34:34.781847Z","pmid":"32737148","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":[]}