ArticleBMC cancer2016
Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse host, and drug schedule dependence of gene responses and their upstream regulators.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Pharmacodynamic biomarkers in metronomic chemotherapy: multiplex cytokine measurements in gastrointestinal cancer patients.Clinical and experimental medicine · 2021Trial
- Calcium Electrochemotherapy and Challenges in Combined Treatment with Dendritic Cell Vaccination.Pharmaceutics · 2025Article
- Synergistic effects of herpes oncolytic virus and cyclophosphamide for recurrent malignant glioma: a narrative review.Annals of medicine and surgery (2012) · 2024Review
- Chemo-Immunotherapy: A New Trend in Cancer Treatment.Cancers · 2023Review
- First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1).Journal for immunotherapy of cancer · 2023Article
- Immunogenic chemotherapy: great potential for improving response rates.Frontiers in oncology · 2023Review
- Cyclophosphamide augments the efficacy ofFrontiers in oncology · 2023Article
- Immunogenic Cell Death Enhances Immunotherapy of Diffuse Intrinsic Pontine Glioma: From Preclinical to Clinical Studies.Pharmaceutics · 2022Review
- Type-I interferon signaling is essential for robust metronomic chemo-immunogenic tumor regression in murine breast cancer.Cancer research communications · 2022Article
- Partially replacing cyclophosphamide with bendamustine in combination with cyclosporine A improves survival and reduces xenogeneic graft-versus-host-disease.Frontiers in immunology · 2022Article
- Advances in CRISPR/Cas9.BioMed research international · 2022Review
- Chemotherapy reinforces anti-tumor immune response and enhances clinical efficacy of immune checkpoint inhibitors.Frontiers in oncology · 2022Review
- Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells.International journal of molecular sciences · 2021Article
- Research on CRISPR/system in major cancers and its potential in cancer treatments.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma.Cancers · 2020Review
- Medium dose intermittent cyclophosphamide induces immunogenic cell death and cancer cell autonomous type I interferon production in glioma models.Cancer letters · 2020Article
- Immunostimulatory and anti-tumor metronomic cyclophosphamide regimens assessed in primary orthotopic and metastatic murine breast cancer.NPJ breast cancer · 2020Article
- Delicate Balances in Cancer Chemotherapy: Modeling Immune Recruitment and Emergence of Systemic Drug Resistance.Frontiers in immunology · 2020Article
- Article
- Immunogenic chemotherapy: Dose and schedule dependence and combination with immunotherapy.Cancer letters · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCyclophosphamide (CPA) can activate immunogenic tumor cell death, which induces immune-based tumor ablation and long-term anti-tumor immunity in a syngeneic C57BL/6 (B6) mouse GL261 glioma model when CPA is given on a 6-day repeating metronomic schedule (CPA/6d). In contrast, we find that two other syngeneic B6 mouse tumors, LLC lung carcinoma and B16F10 melanoma, do not exhibit these drug-induced immune responses despite their intrinsic sensitivity to CPA cytotoxicity.
methodsTo elucidate underlying mechanisms, we investigated gene expression and molecular pathway changes associated with the disparate immune responsiveness of these tumors to CPA/6d treatment.
resultsGlobal transcriptome analysis indicated substantial elevation of basal GL261 immune infiltration and strong CPA/6d activation of GL261 immune stimulatory pathways and their upstream regulators, but without preferential depletion of negative immune regulators compared to LLC and B16F10 tumors. In LLC tumors, where CPA/6d treatment is shown to be anti-angiogenic, CPA/6d suppressed VEGFA target genes and down regulated cell adhesion and leukocyte transendothelial migration genes. In GL261 tumors implanted in adaptive immune-deficient scid mice, where CPA/6d-induced GL261 regression is incomplete and late tumor growth rebound can occur, T cell receptor signaling and certain cytokine-cytokine receptor responses seen in B6 mice were deficient. Extending the CPA treatment interval from 6 to 9 days (CPA/9d) - which results in a strong but transient natural killer cell response followed by early tumor growth rebound - induced fewer cytokines and increased expression of drug metabolism genes.
conclusionsThese findings elucidate molecular response pathways activated by intermittent metronomic CPA treatment and identify deficiencies that characterize immune-unresponsive tumor models and drug schedules.
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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.