{"doi":"10.21037/tlcr-24-284","title":"Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma","abstract":"Background: Anti-tumor CD8 T cells are important for immunity but can become ‘exhausted’ and hence ineffective. Tumor-infiltrating exhausted CD8+ T cells include less differentiated stem-like exhausted T (Texstem) cells and terminally exhausted T (Texterm) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort. Methods: Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Texstem and Texterm CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire. Results: Higher frequency of Texstem was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16–0.79, P=0.01]. The frequency of Texterm was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Texstem, median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10–0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Texstem cells also contained ‘bystander’ virus-specific T cells. Conclusions: This study demonstrates that PE CD8 Texstem cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.","journal":"Translational Lung Cancer Research","year":2024,"id":445613,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"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":722047,"name":"Heeju Ryu","orcid":"0000-0002-4742-5415","position":1,"is_corresponding":false},{"id":567723,"name":"David Granadier","orcid":"0000-0002-1983-4190","position":2,"is_corresponding":false},{"id":1261974,"name":"Long Nguyen","orcid":"0000-0003-0484-7025","position":3,"is_corresponding":false},{"id":256185,"name":"Yannick Simoni","orcid":"0000-0002-9086-3680","position":4,"is_corresponding":false},{"id":1261975,"name":"Ian M. Dick","orcid":"0000-0003-1902-9033","position":5,"is_corresponding":false},{"id":1262451,"name":"Tina Firth","orcid":null,"position":6,"is_corresponding":false},{"id":1262452,"name":"Ebony J. Rouse","orcid":null,"position":7,"is_corresponding":false},{"id":1262453,"name":"Peter K. Chiang","orcid":null,"position":8,"is_corresponding":false},{"id":1262454,"name":"Y. C. Gary Lee","orcid":null,"position":9,"is_corresponding":false},{"id":70131,"name":"Bruce Robinson","orcid":"0000-0002-5281-7923","position":10,"is_corresponding":false},{"id":70130,"name":"Jenette Creaney","orcid":"0000-0002-9391-9395","position":11,"is_corresponding":false},{"id":272540,"name":"Evan W. Newell","orcid":"0000-0002-2889-243X","position":12,"is_corresponding":false},{"id":499250,"name":"Alec Redwood","orcid":"0000-0001-8601-8292","position":13,"is_corresponding":false},{"id":1094073,"name":"Linda Ye","orcid":"0000-0002-0353-4265","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:46.243344Z","pmid":"39430319","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":[]}