{"doi":"10.1038/s41586-023-06231-0","title":"B-cell-specific checkpoint molecules that regulate anti-tumour immunity","abstract":"The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth<sup>1,2</sup>. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.","journal":"Nature","year":2023,"id":7692,"datarank":0.7444266945389861,"base_score":4.962844630259907,"endowment":4.962844630259907,"self_citation_contribution":0.7444266945389861,"citation_network_contribution":0.0,"self_endowment_contribution":0.7444266945389861,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":142,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.044,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-06-21","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":69333,"name":"Yoon-Chul Kye","orcid":"0000-0003-0261-5247","position":1,"is_corresponding":false},{"id":69334,"name":"Jingwen Shi","orcid":"0000-0002-4802-0727","position":2,"is_corresponding":false},{"id":69335,"name":"Elena Torlai Triglia","orcid":"0000-0002-6059-0116","position":3,"is_corresponding":false},{"id":14737,"name":"Alexandra Schnell","orcid":"0000-0003-3442-7750","position":4,"is_corresponding":false},{"id":6931,"name":"Johannes Fessler","orcid":"0000-0002-8841-3795","position":5,"is_corresponding":false},{"id":69336,"name":"Stephen M. Ostrowski","orcid":"0000-0002-0669-7502","position":6,"is_corresponding":false},{"id":69337,"name":"Max Y. Von-Franque","orcid":"0000-0002-5232-6454","position":7,"is_corresponding":false},{"id":69338,"name":"Juhi R. Kuchroo","orcid":"0000-0001-9033-3420","position":8,"is_corresponding":false},{"id":50392,"name":"Rocky M. Barilla","orcid":"0000-0002-8062-7246","position":9,"is_corresponding":false},{"id":6930,"name":"Sarah Zaghouani","orcid":"0000-0002-4467-6542","position":10,"is_corresponding":false},{"id":37423,"name":"Elena Christian","orcid":"0000-0002-5593-0155","position":11,"is_corresponding":false},{"id":7838,"name":"Toni Marie Delorey","orcid":"0000-0001-6614-3803","position":12,"is_corresponding":false},{"id":69339,"name":"Kanishka Mohib","orcid":"0000-0002-7332-5530","position":13,"is_corresponding":false},{"id":7856,"name":"Sheng Xiao","orcid":"0000-0001-6252-8204","position":14,"is_corresponding":false},{"id":69340,"name":"Nadine Slingerland","orcid":"0000-0002-3134-6472","position":15,"is_corresponding":false},{"id":69341,"name":"Christopher J. Giuliano","orcid":"0000-0002-0586-6095","position":16,"is_corresponding":false},{"id":2691,"name":"Orr Ashenberg","orcid":"0000-0002-7802-8834","position":17,"is_corresponding":false},{"id":69342,"name":"Zhaorong Li","orcid":"0000-0002-5268-6986","position":18,"is_corresponding":false},{"id":69343,"name":"David M. Rothstein","orcid":"0000-0002-9455-7971","position":19,"is_corresponding":false},{"id":69344,"name":"David E. Fisher","orcid":"0000-0002-5506-0575","position":20,"is_corresponding":false},{"id":2697,"name":"Orit Rozenblatt–Rosen","orcid":"0000-0001-6313-3570","position":21,"is_corresponding":false},{"id":4542,"name":"Arlene H. Sharpe","orcid":"0000-0002-9736-2109","position":22,"is_corresponding":false},{"id":18937,"name":"Francisco J. Quintana","orcid":"0000-0001-8156-0736","position":23,"is_corresponding":false},{"id":51575,"name":"Lionel Apétoh","orcid":"0000-0002-2774-438X","position":24,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":25,"is_corresponding":false},{"id":6940,"name":"Vijay K. Kuchroo","orcid":"0000-0001-7177-2110","position":26,"is_corresponding":false},{"id":16002,"name":"Lloyd Bod","orcid":"0000-0001-8124-0863","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}