{"doi":"10.1016/j.immuni.2018.11.014","title":"Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells","abstract":"An improved understanding of the anti-tumor CD8<sup>+</sup> T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8<sup>+</sup> TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1<sup>-</sup> TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8<sup>+</sup> T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7/Tcf1 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8<sup>+</sup> T cell responses upon immunotherapy.","journal":"Immunity","year":2019,"id":8980,"datarank":0.9722365693914647,"base_score":6.481577129276431,"endowment":6.481577129276431,"self_citation_contribution":0.9722365693914647,"citation_network_contribution":0.0,"self_endowment_contribution":0.9722365693914647,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":652,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0399,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2019-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7864,"name":"Asaf Madi","orcid":"0000-0003-3441-3228","position":1,"is_corresponding":false},{"id":50393,"name":"Giulia Escobar","orcid":"0000-0001-9177-0251","position":2,"is_corresponding":false},{"id":59675,"name":"Max Klapholz","orcid":"0000-0001-6527-8722","position":3,"is_corresponding":false},{"id":14738,"name":"Jackson Nyman","orcid":"0000-0001-6151-6930","position":4,"is_corresponding":false},{"id":37423,"name":"Elena Christian","orcid":"0000-0002-5593-0155","position":5,"is_corresponding":false},{"id":7858,"name":"Mathias Pawlak","orcid":"0000-0002-4533-398X","position":6,"is_corresponding":false},{"id":2276,"name":"Danielle Dionne","orcid":"0000-0002-8338-4323","position":7,"is_corresponding":false},{"id":51572,"name":"Junrong Xia","orcid":"0000-0002-2818-1494","position":8,"is_corresponding":false},{"id":6940,"name":"Vijay K. Kuchroo","orcid":"0000-0001-7177-2110","position":10,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":11,"is_corresponding":false},{"id":3016,"name":"Ana. C. Anderson","orcid":"0000-0002-0877-2932","position":12,"is_corresponding":false},{"id":58389,"name":"Sema Kurtuluş","orcid":"0000-0002-2842-9437","position":13,"is_corresponding":false},{"id":2697,"name":"Orit Rozenblatt–Rosen","orcid":"0000-0001-6313-3570","position":14,"is_corresponding":false},{"id":58386,"name":"Sema Kurtulus","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}