{"doi":"10.1172/jci.insight.153963","title":"Tumor-infiltrating exhausted CD8+ T cells dictate reduced survival in premenopausal estrogen receptor–positive breast cancer","abstract":"CD8+ tumor-infiltrating lymphocytes (TILs) are associated with improved survival in triple-negative breast cancer (TNBC) yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identified subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX). Tumors with abundant CD8+ TEX exhibited a distinct tumor microenvironment marked by amplified interferon-γ signaling-related pathways and higher programmed death ligand 1 expression. Paradoxically, higher levels of tumor-infiltrating CD8+ TEX associated with decreased overall survival of patients with ER+ BC but not patients with TNBC. Moreover, high tumor expression of a CD8+ TEX signature identified dramatically reduced survival in premenopausal, but not postmenopausal, patients with ER+ BC. Finally, we demonstrated the value of a tumor TEX signature score in identifying high-risk premenopausal ER+ BC patients among those with intermediate Oncotype DX Breast Recurrence Scores. Our data highlight the complex relationship between CD8+ TILs, interferon-γ signaling, and ER status in BC patient survival. This work identifies tumor-infiltrating CD8+ TEX as a key feature of reduced survival outcomes in premenopausal patients with early-stage ER+ BC.","journal":"JCI Insight","year":2022,"id":239915,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"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":660172,"name":"Weihua Guo","orcid":"0000-0002-9580-513X","position":1,"is_corresponding":false},{"id":866426,"name":"Jiayi Tan","orcid":"0000-0001-5938-7471","position":2,"is_corresponding":false},{"id":294147,"name":"Christian Avalos","orcid":"0000-0001-8852-9520","position":3,"is_corresponding":false},{"id":296475,"name":"Diana L. Simons","orcid":null,"position":4,"is_corresponding":false},{"id":866919,"name":"Min Hui Lim","orcid":null,"position":5,"is_corresponding":false},{"id":550295,"name":"Yinghui Huang","orcid":"0000-0003-0974-9539","position":6,"is_corresponding":false},{"id":445747,"name":"Michael S. Nelson","orcid":"0000-0003-0480-5597","position":7,"is_corresponding":false},{"id":289780,"name":"Arnab Chowdhury","orcid":"0000-0003-4683-9242","position":8,"is_corresponding":false},{"id":582368,"name":"Daniel Schmolze","orcid":"0000-0002-6947-2546","position":9,"is_corresponding":false},{"id":296476,"name":"John H. Yim","orcid":null,"position":10,"is_corresponding":false},{"id":461452,"name":"Laura Kruper","orcid":"0000-0002-7268-0354","position":11,"is_corresponding":false},{"id":409403,"name":"Laleh G. Melstrom","orcid":"0000-0001-6279-7981","position":12,"is_corresponding":false},{"id":325116,"name":"Kim Margolin","orcid":"0000-0002-5248-4356","position":13,"is_corresponding":false},{"id":288920,"name":"Joanne Mortimer","orcid":"0000-0002-2935-1934","position":14,"is_corresponding":false},{"id":443405,"name":"Yuan Yuan","orcid":"0000-0001-7440-8939","position":15,"is_corresponding":false},{"id":294149,"name":"James Waisman","orcid":"0000-0003-2896-4146","position":16,"is_corresponding":false},{"id":294150,"name":"Peter P. Lee","orcid":"0000-0002-2660-4377","position":17,"is_corresponding":false},{"id":564708,"name":"Colt A. Egelston","orcid":"0000-0001-8440-1271","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:22:41.699779Z","pmid":"35132960","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":[]}