ArticleCancer science2019
CD47 agonist peptide PKHB1 induces immunogenic cell death in T-cell acute lymphoblastic leukemia cells.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Immunomodulatory role and therapeutic potential of thrombospondin-1 during infectious diseases and autoimmunity.BMC biology · 2026Review
- Thrombospondin-1 triggers calreticulin expression in human mucoepidermoid carcinoma MC-3 cells via the PERK/CHOP pathway.Oncology letters · 2026Article
- Peptide-mediated immunomodulation of tumor microenvironment in triple-negative breast cancer: A comprehensive review.The Journal of pharmacology and experimental therapeutics · 2026Review
- Human Serum Albumin-Lipid Nanocapsules of Duvelisib for Hematological Cancers: Characterization, In-Vitro Cell-Culture, Toxicity and Pharmacokinetic Studies.AAPS PharmSciTech · 2026Article
- The mitochondria as an emerging target of self-renewal in T-cell acute lymphoblastic leukemia.Cancer biology & therapy · 2025Review
- Thrombospondin-1 induces immunogenic cell death in human mucoepidermoid carcinoma MC-3 cells via the PERK/eIF2α signaling pathway: potential implications for tumor immunotherapy.Discover oncology · 2025Article
- Therapeutic strategies targeting CD47-SIRPα signaling pathway in gastrointestinal cancers treatment.Journal of pharmaceutical analysis · 2025Review
- Signature identification based on immunogenic cell death-related lncRNAs to predict the prognosis and immune activity of patients with endometrial carcinoma.Translational cancer research · 2024Article
- Deregulation of New Cell Death Mechanisms in Leukemia.Cancers · 2024Review
- A novel immunogenic cell death-related classification indicates the immune landscape and predicts clinical outcome and treatment response in acute myeloid leukemia.Cancer cell international · 2024Article
- Emerging functions of thrombospondin-1 in immunity.Seminars in cell & developmental biology · 2024Review
- Exploiting cell death and tumor immunity in cancer therapy: challenges and future directions.Frontiers in cell and developmental biology · 2024Review
- Immunopeptides: immunomodulatory strategies and prospects for ocular immunity applications.Frontiers in immunology · 2024Review
- Dual Role of Vitamin C-Encapsulated Liposomal Berberine in Effective Colon Anticancer Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis.Scientific reports · 2023Article
- Immunogenic Cell Death in Hematological Malignancy Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies.Nanoscale advances · 2023Review
- Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system.Frontiers in immunology · 2023Review
- Trial watch: chemotherapy-induced immunogenic cell death in oncology.Oncoimmunology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis derived from its genetic heterogeneity, which translates to a high chemoresistance. Recently, our workgroup designed thrombospondin-1-derived CD47 agonist peptides and demonstrated their ability to induce cell death in chronic lymphocytic leukemia. Encouraged by these promising results, we evaluated cell death induced by PKHB1 (the first-described serum-stable CD47-agonist peptide) on CEM and MOLT-4 human cell lines (T-ALL) and on one T-murine tumor lymphoblast cell-line (L5178Y-R), also assessing caspase and calcium dependency and mitochondrial membrane potential. Additionally, we evaluated selectivity for cancer cell lines by analyzing cell death and viability of human and murine non-tumor cells after CD47 activation. In vivo, we determined that PKHB1-treatment in mice bearing the L5178Y-R cell line increased leukocyte cell count in peripheral blood and lymphoid organs while recruiting leukocytes to the tumor site. To analyze whether CD47 activation induced immunogenic cell death (ICD), we evaluated damage-associated molecular patterns (DAMP) exposure (calreticulin, CRT) and release (ATP, heat shock proteins 70 and 90, high-mobility group box 1, CRT). Furthermore, we gave prophylactic antitumor vaccination, determining immunological memory. Our data indicate that PKHB1 induces caspase-independent and calcium-dependent cell death in leukemic cells while sparing non-tumor murine and human cells. Moreover, our results show that PKHB1 can induce ICD in leukemic cells as it induces CRT exposure and DAMP release in vitro, and prophylactic vaccinations inhibit tumor establishment in vivo. Together, our results improve the knowledge of CD47 agonist peptides potential as therapeutic tools to treat leukemia.
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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.