{"doi":"10.1101/2023.01.01.522340","title":"KLRG1 marks tumor-infiltrating CD4 T cell subsets associated with tumor progression and immunotherapy response","abstract":"Abstract Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios - KLRG1 + subset of tumor-infiltrating regulatory T cells (Tregs) was associated with tumor progression from immune equilibrium to escape, and were also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumorinfiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1 + CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker and/or target discovery.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398066,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9433,"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":1063696,"name":"Mingxuan Zhang","orcid":"0000-0001-9371-793X","position":1,"is_corresponding":false},{"id":269200,"name":"Matthew G. Chaimowitz","orcid":null,"position":2,"is_corresponding":false},{"id":937687,"name":"Shruti Bansal","orcid":null,"position":3,"is_corresponding":false},{"id":266898,"name":"Aleksandar Obradović","orcid":"0000-0002-8009-0186","position":4,"is_corresponding":false},{"id":98182,"name":"Meri Rogava","orcid":"0000-0002-0314-5323","position":5,"is_corresponding":false},{"id":24144,"name":"Johannes C. Melms","orcid":"0000-0002-5410-6586","position":6,"is_corresponding":false},{"id":377550,"name":"Patrick McCann","orcid":null,"position":7,"is_corresponding":false},{"id":266901,"name":"Catherine S. Spina","orcid":"0000-0001-6067-5024","position":8,"is_corresponding":false},{"id":59423,"name":"Charles G. Drake","orcid":"0000-0001-9610-3677","position":9,"is_corresponding":false},{"id":266902,"name":"Matthew C. Dallos","orcid":"0000-0002-5412-3490","position":10,"is_corresponding":false},{"id":5593,"name":"Benjamin Izar","orcid":"0000-0003-2379-6702","position":11,"is_corresponding":false},{"id":266897,"name":"Casey R. Ager","orcid":"0000-0003-0507-700X","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:43.776284Z","pmid":"36711647","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":[]}