{"doi":"10.1101/2020.10.22.350934","title":"Lymphatic PD-L1 expression restricts tumor-specific CD8 <sup>+</sup> T cell responses","abstract":"ABSTRACT Lymph node (LN)-resident lymphatic endothelial cells (LECs) mediate peripheral tolerance by self-antigen presentation on MHC-I and constitutive expression of T cell inhibitory molecules, including PD-L1. Tumor-associated LECs also upregulate PD-L1 but the specific role of lymphatic PD-L1 in tumor immunity is not well understood. We generated a mouse model lacking lymphatic PD-L1 expression and challenged these mice with two orthotopic tumor models, B16F10 melanoma and MC38 colorectal carcinoma. Lymphatic PD-L1 deficiency resulted in a consistent expansion of tumor-specific CD8 + T cells in tumor-draining LNs in both tumor models, reduced primary tumor growth in the MC38 model, and increased the efficacy of adoptive T cell therapy in the B16F10 model. Strikingly, lymphatic PD-L1 primarily acted via apoptosis induction in tumor-specific CD8 + central memory T cells. Our findings demonstrate that LECs restrain tumor-specific immunity via PD-L1 and may explain why some cancer patients without PD-L1 expression in the tumor microenvironment still respond to PD-L1 / PD-1 targeting immunotherapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127531,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"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":577823,"name":"Stefan Cap","orcid":null,"position":1,"is_corresponding":false},{"id":577824,"name":"Manuel Dihr","orcid":null,"position":2,"is_corresponding":false},{"id":576813,"name":"Carlotta Tacconi","orcid":"0000-0002-6431-7555","position":3,"is_corresponding":false},{"id":77620,"name":"Michael Detmar","orcid":"0000-0002-5351-5054","position":4,"is_corresponding":false},{"id":576814,"name":"Lothar C. Dieterich","orcid":"0000-0001-7908-5710","position":5,"is_corresponding":false},{"id":576812,"name":"Nikola Cousin","orcid":"0000-0002-1237-1429","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:15:34.966380Z","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":[]}