{"doi":"10.1172/jci155148","title":"Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-β signaling enables PD-L1–mediated tumor eradication","abstract":"Collagens in the extracellular matrix (ECM) provide a physical barrier to tumor immune infiltration, while also acting as a ligand for immune inhibitory receptors. Transforming growth factor-β (TGF-β) is a key contributor to shaping the ECM by stimulating the production and remodeling of collagens. TGF-β activation signatures and collagen-rich environments have both been associated with T cell exclusion and lack of responses to immunotherapy. Here, we describe the effect of targeting collagens that signal through the inhibitory leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in combination with blockade of TGF-β and programmed cell death ligand 1 (PD-L1). This approach remodeled the tumor collagenous matrix, enhanced tumor infiltration and activation of CD8+ T cells, and repolarized suppressive macrophage populations, resulting in high cure rates and long-term tumor-specific protection across murine models of colon and mammary carcinoma. The results highlight the advantage of direct targeting of ECM components in combination with immune checkpoint blockade therapy.","journal":"Journal of Clinical Investigation","year":2022,"id":233677,"datarank":2.8826288241219546,"base_score":4.787491742782046,"endowment":4.787491742782046,"self_citation_contribution":0.7181237614173069,"citation_network_contribution":2.164505062704648,"self_endowment_contribution":0.7181237614173069,"citer_contribution":2.164505062704648,"corpus_percentile":null,"corpus_rank":null,"citation_count":119,"citer_count":100,"citers_with_citation_signal":98,"citers_with_endowment":98,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00001846"]},"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":246023,"name":"Paul L. Chariou","orcid":"0000-0002-7115-3878","position":1,"is_corresponding":false},{"id":239938,"name":"Sofia R. Gameiro","orcid":"0000-0002-2392-8122","position":2,"is_corresponding":false},{"id":831899,"name":"Haiyan Qin","orcid":"0000-0003-3731-5236","position":3,"is_corresponding":false},{"id":847888,"name":"Masafumi Iida","orcid":"0000-0003-0095-9767","position":4,"is_corresponding":false},{"id":231604,"name":"Kristen Fousek","orcid":"0000-0002-2307-5000","position":5,"is_corresponding":false},{"id":500995,"name":"Thomas J. Meyer","orcid":"0000-0002-7185-5597","position":6,"is_corresponding":false},{"id":349715,"name":"Margaret C. Cam","orcid":null,"position":7,"is_corresponding":false},{"id":847889,"name":"Dallas B. Flies","orcid":"0000-0002-9280-2080","position":8,"is_corresponding":false},{"id":847890,"name":"Solomon Langermann","orcid":"0000-0002-9596-4931","position":9,"is_corresponding":false},{"id":239943,"name":"Jeffrey Schlom","orcid":"0000-0001-7932-4072","position":10,"is_corresponding":false},{"id":231605,"name":"Claudia Palena","orcid":"0000-0002-0445-4486","position":11,"is_corresponding":false},{"id":234208,"name":"Lucas A. Horn","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:21:31.237180Z","pmid":"35230974","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":[]}