{"doi":"10.1158/2159-8290.cd-21-0694","title":"PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity","abstract":"Immunotherapies aimed at alleviating the inhibitory constraints on T cells have revolutionized cancer management. To date, these have focused on the blockade of cell-surface checkpoints such as PD-1. Herein we identify protein tyrosine phosphatase 1B (PTP1B) as an intracellular checkpoint that is upregulated in T cells in tumors. We show that increased PTP1B limits T-cell expansion and cytotoxicity to contribute to tumor growth. T cell-specific PTP1B deletion increased STAT5 signaling, and this enhanced the antigen-induced expansion and cytotoxicity of CD8+ T cells to suppress tumor growth. The pharmacologic inhibition of PTP1B recapitulated the T cell-mediated repression of tumor growth and enhanced the response to PD-1 blockade. Furthermore, the deletion or inhibition of PTP1B enhanced the efficacy of adoptively transferred chimeric antigen receptor (CAR) T cells against solid tumors. Our findings identify PTP1B as an intracellular checkpoint whose inhibition can alleviate the inhibitory constraints on T cells and CAR T cells to combat cancer. SIGNIFICANCE: Tumors subvert antitumor immunity by engaging checkpoints that promote T-cell exhaustion. Here we identify PTP1B as an intracellular checkpoint and therapeutic target. We show that PTP1B is upregulated in intratumoral T cells and that its deletion or inhibition enhances T-cell antitumor activity and increases CAR T-cell effectiveness against solid tumors. This article is highlighted in the In This Issue feature, p. 587.","journal":"Cancer Discovery","year":2021,"id":148040,"datarank":0.7401710899696038,"base_score":4.9344739331306915,"endowment":4.9344739331306915,"self_citation_contribution":0.7401710899696038,"citation_network_contribution":0.0,"self_endowment_contribution":0.7401710899696038,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":138,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":630025,"name":"Kun‐Hui Lu","orcid":"0000-0003-2505-6513","position":1,"is_corresponding":false},{"id":630026,"name":"Xin Du","orcid":"0000-0002-9682-1211","position":2,"is_corresponding":false},{"id":630027,"name":"Mara N. Zeissig","orcid":"0000-0003-3264-6546","position":3,"is_corresponding":false},{"id":631305,"name":"Rachel Xu","orcid":null,"position":4,"is_corresponding":false},{"id":630028,"name":"Pei Kee Goh","orcid":"0000-0001-9404-6058","position":5,"is_corresponding":false},{"id":630029,"name":"Chrysovalantou E. Xirouchaki","orcid":"0000-0002-8153-8958","position":6,"is_corresponding":false},{"id":630030,"name":"Samuel J. Hogarth","orcid":"0000-0001-7681-0518","position":7,"is_corresponding":false},{"id":631306,"name":"Spencer Greatorex","orcid":null,"position":8,"is_corresponding":false},{"id":630031,"name":"Kevin Sek","orcid":"0000-0003-4634-7600","position":9,"is_corresponding":false},{"id":267339,"name":"Roger J. Daly","orcid":"0000-0002-5739-8027","position":10,"is_corresponding":false},{"id":630032,"name":"Paul A. Beavis","orcid":"0000-0002-2116-013X","position":11,"is_corresponding":false},{"id":630033,"name":"Phillip K. Darcy","orcid":"0000-0002-5303-9561","position":12,"is_corresponding":false},{"id":614542,"name":"Nicholas K. Tonks","orcid":"0000-0002-2394-1538","position":13,"is_corresponding":false},{"id":630034,"name":"Tony Tiganis","orcid":"0000-0002-8065-9942","position":14,"is_corresponding":false},{"id":630024,"name":"Florian Wiede","orcid":"0000-0001-5145-7180","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:41.063423Z","pmid":"34794959","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":[]}