{"doi":"10.1101/2023.12.08.570738","title":"Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity","abstract":"SUMMARY Signals emanating from the T cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T cell function. Through forward genetic screening in mice, we discovered that loss-of-function mutations in LDL receptor related protein 10 ( Lrp10 ) caused naïve and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. Lrp10 was induced with T cell activation and its expression post-translationally suppressed IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhanced T cell homeostatic expansion through IL7R signaling. Lrp10 -deficient mice were also intrinsically resistant to syngeneic tumors. This phenotype depended on dense tumor infiltration of CD8 T cells that displayed increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":414876,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1196790,"name":"Luming Chen","orcid":"0000-0003-0852-5752","position":1,"is_corresponding":false},{"id":395801,"name":"Aijie Liu","orcid":"0000-0002-4777-7795","position":2,"is_corresponding":false},{"id":368856,"name":"Jianhui Wang","orcid":"0000-0002-6335-8355","position":3,"is_corresponding":false},{"id":1196791,"name":"Subarna Ghosh","orcid":"0000-0002-7956-1788","position":4,"is_corresponding":false},{"id":108776,"name":"Xue Zhong","orcid":"0000-0001-6039-1793","position":5,"is_corresponding":false},{"id":576803,"name":"Hexin Shi","orcid":"0000-0001-8075-511X","position":6,"is_corresponding":false},{"id":51949,"name":"Bruce Beutler","orcid":"0000-0002-3639-246X","position":7,"is_corresponding":false},{"id":395804,"name":"Evan Nair‐Gill","orcid":"0000-0002-9876-7853","position":8,"is_corresponding":false},{"id":1197107,"name":"Jamie Russell","orcid":null,"position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:22:08.814145Z","pmid":"38106103","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":[]}