{"doi":"10.1126/sciimmunol.adi7418","title":"LRIG1 engages ligand VISTA and impairs tumor-specific CD8 <sup>+</sup> T cell responses","abstract":"Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell–specific LRIG1 deletion developed superior antitumor responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1 + CD62L hi PD-1 low ) and a reciprocal increase in progenitor and memory-like CTLs (TCF1 + PD-1 + ). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8 + CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.","journal":"Science Immunology","year":2024,"id":419248,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":1010723,"name":"Dia Roy","orcid":"0000-0002-5036-7009","position":1,"is_corresponding":false},{"id":749327,"name":"Keman Zhang","orcid":"0000-0002-1872-2875","position":2,"is_corresponding":false},{"id":240685,"name":"Tyler Alban","orcid":"0000-0002-3261-140X","position":3,"is_corresponding":false},{"id":254656,"name":"Ivan Jurić","orcid":"0000-0002-1076-6320","position":4,"is_corresponding":false},{"id":1208650,"name":"Juan Dong","orcid":"0000-0002-3070-9972","position":5,"is_corresponding":false},{"id":854207,"name":"Prerana Bangalore Parthasarathy","orcid":"0009-0002-7702-9656","position":6,"is_corresponding":false},{"id":1208651,"name":"Sachin Patnaik","orcid":"0009-0000-3610-5259","position":7,"is_corresponding":false},{"id":1208652,"name":"Elizabeth Delaney","orcid":"0000-0003-3956-7920","position":8,"is_corresponding":false},{"id":1010725,"name":"Cassandra Gilmour","orcid":"0000-0003-4885-2862","position":9,"is_corresponding":false},{"id":1208653,"name":"Amin Zakeri","orcid":"0000-0001-7961-0634","position":10,"is_corresponding":false},{"id":672469,"name":"Nidhi Shukla","orcid":"0000-0001-5912-7039","position":11,"is_corresponding":false},{"id":702053,"name":"Amit Rupani","orcid":"0000-0002-2502-7926","position":12,"is_corresponding":false},{"id":893696,"name":"Yee Peng Phoon","orcid":null,"position":13,"is_corresponding":false},{"id":292271,"name":"Caini Liu","orcid":"0000-0002-9314-7145","position":14,"is_corresponding":false},{"id":464190,"name":"Stefanie Avril","orcid":"0000-0002-3394-8733","position":15,"is_corresponding":false},{"id":864584,"name":"Brian Gastman","orcid":"0000-0003-2691-3409","position":16,"is_corresponding":false},{"id":69956,"name":"Timothy A. Chan","orcid":"0000-0002-9265-0283","position":17,"is_corresponding":false},{"id":1208654,"name":"Li Lily Wang","orcid":"0000-0002-3088-3022","position":18,"is_corresponding":false},{"id":1010724,"name":"Hieu Minh Ta","orcid":"0000-0003-2569-1648","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:57:14.586331Z","pmid":"38758807","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":[]}