ArticleCancer immunology, immunotherapy : CII2010
Hematopoietic progenitor kinase 1 is a critical component of prostaglandin E2-mediated suppression of the anti-tumor immune response.
Article in Cancer immunology, immunotherapy : CII, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 70 citations in OpenAlex.
- HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase 1/2 trial results.Cell reports. Medicine · 2026Trial
- 7-azaindole as privileged scaffold: Advances in drug design and structural modification.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- From inhibition to degradation: advances in highly selective targeting strategies for HPK1.Molecular diversity · 2026Review
- CISH, a key intracellular checkpoint, in comparison and combination to existing and emerging cancer immune checkpoints.Communications biology · 2026Article
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Highly selective HPK1 inhibitor NDI-101150 mediates immune cell activation and robust antitumor responses, distinct from immune checkpoint blockade.Journal for immunotherapy of cancer · 2025Article
- Design, Synthesis, and Biological Evaluation of a Series of Spiro Analogues as Novel HPK1 Inhibitors.ACS medicinal chemistry letters · 2024Article
- Discovery of BAY-405: An Azaindole-Based MAP4K1 Inhibitor for the Enhancement of T-Cell Immunity against Cancer.Journal of medicinal chemistry · 2024Article
- HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An updated review of small-molecule HPK1 kinase inhibitors (2016-present).Future medicinal chemistry · 2024Review
- Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Theoretical Studies on Selectivity of HPK1/JAK1 Inhibitors by Molecular Dynamics Simulations and Free Energy Calculations.International journal of molecular sciences · 2023Article
- Genome Editing for Engineering the Next Generation of Advanced Immune Cell Therapies.Advances in experimental medicine and biology · 2023Article
- Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.Frontiers in immunology · 2023Review
- The expanding role for small molecules in immuno-oncology.Nature reviews. Drug discovery · 2022Review
- Decreased Jumonji Domain-Containing 3 at the Promoter Downregulates Hematopoietic Progenitor Kinase 1 Expression and Cytoactivity of T Follicular Helper Cells from Systemic Lupus Erythematosus Patients.Journal of immunology research · 2022Article
- Identification of Potent Reverse Indazole Inhibitors for HPK1.ACS medicinal chemistry letters · 2021Article
- Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1).Acta crystallographica. Section F, Structural biology communications · 2021Article
- Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Lung cancer is the leading cause of cancer-related mortality in the world, resulting in over a million deaths each year. Non-small cell lung cancers (NSCLCs) are characterized by a poor immunogenic response, which may be the result of immunosuppressive factors such as prostaglandin E2 (PGE(2)) present in the tumor environment. The effect of PGE(2) in the suppression of anti-tumor immunity and its promotion of tumor survival has been established for over three decades, but with limited mechanistic understanding. We have previously reported that PGE(2) activates hematopoietic progenitor kinase 1 (HPK1), a hematopoietic-specific kinase known to negatively regulate T-cell receptor signaling. Here, we report that mice genetically lacking HPK1 resist the growth of PGE(2)-producing Lewis lung carcinoma (LLC). The presence of tumor-infiltrating lymphocytes (TILs) and T-cell transfer into T cell-deficient mice revealed that tumor rejection is T cell mediated. Further analysis demonstrated that this may be significantly due to the ability of HPK1 (-/-) T cells to withstand PGE(2)-mediated suppression of T-cell proliferation, IL-2 production, and apoptosis. We conclude that PGE(2) utilizes HPK1 to suppress T cell-mediated anti-tumor responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.