{"doi":"10.1136/jitc-2021-003571","title":"TIM-3 blockade enhances IL-12-dependent antitumor immunity by promoting CD8<sup>+</sup> T cell and XCR1<sup>+</sup> dendritic cell spatial co-localization","abstract":"Background T cell immunoglobulin and mucin domain containing−3 (TIM-3) blocking antibodies are currently being evaluated in clinical trials for solid and hematological malignancies. Despite its identification on T cells, TIM-3 is predominantly expressed by myeloid cells, including XCR1 + type I conventional dendritic cells (cDC1s). We have recently shown that TIM-3 blockade promotes expression of CXCR3 chemokine ligands by tumor cDCs, but how this drives a CD8 + T cell-dependent response to therapy is unclear. Methods T cell infiltration, effector function, and spatial localization in relation to XCR1 + cDC1s were evaluated in a murine orthotopic mammary carcinoma model during response to TIM-3 blockade and paclitaxel chemotherapy. Mixed bone marrow chimeras and diphtheria toxin depletion were used to determine the role of specific genes in cDC1s during therapeutic responses. Results TIM-3 blockade increased interferon-γ expression by CD8 + T cells without altering immune infiltration. cDC1 expression of CXCL9, but not CXCL10, was required for response to TIM-3 blockade. CXCL9 was also necessary for the increased proximity observed between CD8 + T cells and XCR1 + cDC1s during therapy. Tumor responses were dependent on cDC1 expression of interleukin-12, but not MHCI. Conclusions TIM-3 blockade increases exposure of intratumoral CD8 + T cells to cDC1-derived cytokines, with implications for the design of therapeutic strategies using antibodies against TIM-3.","journal":"Journal for ImmunoTherapy of Cancer","year":2022,"id":238778,"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":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"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":227259,"name":"Álvaro de Mingo Pulido","orcid":"0000-0001-9814-1837","position":1,"is_corresponding":false},{"id":242934,"name":"Kay Hänggi","orcid":"0000-0003-1435-3707","position":2,"is_corresponding":false},{"id":457862,"name":"Sarah Bazargan","orcid":null,"position":3,"is_corresponding":false},{"id":621047,"name":"Alexis Onimus","orcid":"0000-0002-5764-6238","position":4,"is_corresponding":false},{"id":863982,"name":"Agnieszka Kasprzak","orcid":null,"position":5,"is_corresponding":false},{"id":242941,"name":"José R. Conejo-García","orcid":"0000-0001-6431-4074","position":6,"is_corresponding":false},{"id":267807,"name":"Katarzyna A. Rejniak","orcid":"0000-0003-2093-2422","position":7,"is_corresponding":false},{"id":227260,"name":"Brian Ruffell","orcid":"0000-0002-3846-6872","position":8,"is_corresponding":false},{"id":227258,"name":"Alycia Gardner","orcid":"0000-0003-2185-5174","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:22:31.741535Z","pmid":"34987021","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":[]}