{"doi":"10.1093/intimm/dxac038","title":"CD8 T-cell heterogeneity during T-cell exhaustion and PD-1-targeted immunotherapy","abstract":"Persistent antigenic stimulation results in loss of effector function or physical deletion of antigen-specific CD8 T cells. This T-cell state is called T-cell exhaustion and occurs during chronic infection and cancer. Antigen-specific CD8 T cells during T-cell exhaustion express the inhibitory receptor PD-1, the expression of which plays a major role in T-cell dysfunction. PD-1 blockade re-invigorates CD8 T-cell immunity and has been proven effective against many different types of human cancer. To further improve the efficacy of PD-1-targeted immunotherapy in cancer patients, a better understanding of T-cell exhaustion is required. Recent studies have revealed that antigen-specific CD8 T cells during T-cell exhaustion are heterogeneous and have also uncovered the detailed mechanisms for PD-1-targeted immunotherapy. Here, we review the CD8 T-cell subsets that arise during T-cell exhaustion, the lineage relationship among these individual subsets and the role of each subset in PD-1 blockade. Also, we discuss potential strategies to enhance the efficacy of PD-1-targeted immunotherapy.","journal":"International Immunology","year":2022,"id":242895,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"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":504867,"name":"Koichi Araki","orcid":"0000-0003-3478-6315","position":1,"is_corresponding":false},{"id":504863,"name":"Satomi Ando","orcid":"0009-0008-7149-8412","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T00:23:10.218426Z","pmid":"35901837","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":[]}