{"doi":"10.1101/2022.01.24.477554","title":"CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer","abstract":"ABSTRACT The repertoire of tumor-infiltrating lymphocytes (TILs) can be vast, and many of these TILs are not endowed with tumor reactivity. While a number of reports have shown that tumor-reactive TILs express CD39, few reports have demonstrated that conversely, CD39 can be leveraged to serve as a proxy of tumor-reactive CD8 T cells. Using single-cell CITE/RNA/TCRseq, we show that CD39 + CD8 T cells in human lung cancers demonstrate transcriptional and proteomic features of exhaustion, tumor reactivity, and clonal expansion. Moreover, TCR cloning revealed that CD39 enriched for tumor-reactive CD8 T cell clones. Flow cytometry of 440 lung cancer specimens revealed that CD39 level on CD8 T cells is only weakly correlated with tumoral features that currently guide lung cancer therapy, such as histology, driver mutation, PD-L1 and tumor mutation burden. PD-1 axis blockade, but not cytotoxic chemotherapy, increased intratumoral CD39 + CD8 T cells. CD39 correlated with PD-1 expression on CD8 T cells and high pre-treatment/early-on-treatment levels were associated with improved clinical outcomes, but not immune-related adverse events, from immune checkpoint blockade therapy. This comprehensive profiling of the clinical, pathological and molecular features highlights the utility of CD39 as a proxy for tumor-reactive CD8 T cells in human lung cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299803,"datarank":0.2403164126007283,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.032372258432744695,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.032372258432744695,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"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":229270,"name":"Fathema Uddin","orcid":null,"position":1,"is_corresponding":false},{"id":227532,"name":"Levi Mangarin","orcid":"0000-0003-1219-6998","position":2,"is_corresponding":false},{"id":91573,"name":"Hira Rizvi","orcid":"0000-0002-8007-096X","position":3,"is_corresponding":false},{"id":831367,"name":"Anton Dobrin","orcid":"0000-0002-9751-0677","position":4,"is_corresponding":false},{"id":555174,"name":"Sam E. 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