ArticleThe Journal of clinical investigation2021
Systemic inhibition of PTPN22 augments anticancer immunity.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Characterization of persistent HPV-specific activated T cells in head and neck squamous cell carcinoma.Oncoimmunology · 2026Article
- Regression-Associated Macrophages Recruit Natural Killer Cells That Constrain Targeted Therapy Resistance.Cancer research · 2026Article
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- First-in-Class Immuno-Oncology Drug APG157DS Repolarizes Innate Immune Cells and Induces Durable Remission in a Syngeneic Glioblastoma Model.International journal of molecular sciences · 2026Article
- A Potent and Selective Quinolone-Based PTPN22 Inhibitor with Improved Immunotherapeutic Activity.Journal of medicinal chemistry · 2026Article
- Review
- Article
- PTPN22 Dephosphorylates CBL to Inhibit PD-L1 Ubiquitination and Drive Immunosuppression in Renal Cell Carcinoma.International journal of biological sciences · 2026Article
- Immunotherapy drug target identification using machine learning and patient-derived tumour explant validation.Nature machine intelligence · 2026Article
- Type I interferon production in myeloid cells is regulated by factors independent of Ptpn22.ImmunoHorizons · 2025Article
- Article
- The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR.Scientific reports · 2025Article
- Discovery and Evaluation of Active Site-Directed, Potent, and Selective Sulfophenyl Acetic Amide-Based Inhibitors for the Laforin Phosphatase.Journal of medicinal chemistry · 2025Article
- Immune-related genetic single-nucleotide polymorphisms contribute to prognosis and response to chemotherapy in patients with acute lymphoblastic leukemia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- The protein tyrosine phosphatase Lyp/PTPN22 drives TNFα-induced priming of superoxide anions production by neutrophils and arthritis.Free radical biology & medicine · 2025Article
- Structure-activity relationship studies and design of a PTPN22 inhibitor with enhanced isozyme selectivity and cellular efficacy.European journal of medicinal chemistry · 2025Article
- Main Genes Linked to the Immune Microenvironment in High-Grade Serous Ovarian Cancer.Advanced biomedical research · 2025Article
- Dendritic cell-intrinsic PTPN22 negatively regulates antitumor immunity and impacts anti-PD-L1 efficacy.Journal for immunotherapy of cancer · 2024Article
- Androgens contribute to sex bias of autoimmunity in mice by T cell-intrinsic regulation of Ptpn22 phosphatase expression.Nature communications · 2024Article
- Genetic and epigenetic regulation of inflammasomes: Role in atherosclerosis.Atherosclerosis · 2024Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Both epidemiologic and cellular studies in the context of autoimmune diseases have established that protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a key regulator of T cell receptor (TCR) signaling. However, its mechanism of action in tumors and its translatability as a target for cancer immunotherapy have not been established. Here we show that a germline variant of PTPN22, rs2476601, portended a lower likelihood of cancer in patients. PTPN22 expression was also associated with markers of immune regulation in multiple cancer types. In mice, lack of PTPN22 augmented antitumor activity with greater infiltration and activation of macrophages, natural killer (NK) cells, and T cells. Notably, we generated a novel small molecule inhibitor of PTPN22, named L-1, that phenocopied the antitumor effects seen in genotypic PTPN22 knockout. PTPN22 inhibition promoted activation of CD8+ T cells and macrophage subpopulations toward MHC-II expressing M1-like phenotypes, both of which were necessary for successful antitumor efficacy. Increased PD1-PDL1 axis in the setting of PTPN22 inhibition could be further leveraged with PD1 inhibition to augment antitumor effects. Similarly, cancer patients with the rs2476601 variant responded significantly better to checkpoint inhibitor immunotherapy. Our findings suggest that PTPN22 is a druggable systemic target for cancer immunotherapy.
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