ArticleCancer immunology, immunotherapy : CII2013
Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo.
Article in Cancer immunology, immunotherapy : CII, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Pooled it
- Gemcitabine plus Nivolumab with Carboplatin or Oxaliplatin in Cisplatin-Ineligible Patients with Metastatic Urothelial Carcinoma: A Randomized Phase II Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Trial
- Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00.Breast cancer research and treatment · 2016Trial
- Immunogenic Cell Death: Unlocking New Frontiers in Cancer Immunotherapy.Cancer innovation · 2026Review
- Synergistic interactions and optimal sequencing of chemotherapy and immunotherapy in cancer treatment.Cancer chemotherapy and pharmacology · 2026Review
- Cyclophosphamide-Mediated Induction of Myeloid-Derived Suppressor Cells In Vivo: Kinetics of Accumulation, Immune Profile, and Immunomodulation by Oleanane-Type Triterpenoids.International journal of molecular sciences · 2026Article
- Athymic murine models can underestimate the immune-dependent components of chemotherapy efficacy.Frontiers in immunology · 2026Review
- Single-cell transcriptomic profiling of immune landscape in triple-negative breast cancer during neoadjuvant chemotherapy.NPJ systems biology and applications · 2025Article
- Recent Advancement in Drug Targeting Therapies in the Treatment of Pancreatic Cancer.Current pharmaceutical design · 2025Review
- Low-dose metronomic cisplatin as an antiangiogenic and anti-inflammatory strategy for cancer.British journal of cancer · 2024Article
- Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy.Frontiers in cell and developmental biology · 2024Review
- Refurbishment of NK cell effector functions through their receptors by depleting the activity of nTreg cells in Dalton's Lymphoma-induced tumor microenvironment: an in vitro and in vivo study.Cancer immunology, immunotherapy : CII · 2023Article
- Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators.Cancer cell · 2023Article
- Metronomic Chemotherapy: Anti-Tumor Pathways and Combination with Immune Checkpoint Inhibitors.Cancers · 2023Review
- Boosting In-Vivo Anti-Tumor Immunity with an Oral Microparticulate Breast Cancer Vaccine and Low-Dose Cyclophosphamide.Vaccines · 2023Article
- Tackling the dysregulated immune-checkpoints in classical Hodgkin lymphoma: bidirectional regulations between the microenvironment and Hodgkin/Reed-Sternberg cells.Frontiers in oncology · 2023Review
- Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- DNA-double strand breaks enhance the expression of major histocompatibility complex class II through the ATM-NF-κΒ-IRF1-CIITA pathway.Cancer gene therapy · 2022Article
- Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.Molecular cancer · 2022Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several chemotherapeutic drugs have immune-modulating effects. For example, cyclophosphamide (CP) and gemcitabine (GEM) diminish immunosuppression by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), respectively. Here, we show that intermittent (metronomic) chemotherapy with low-dose CP plus GEM can induce anti-tumor T cell immunity in CT26 colon carcinoma-bearing mice. Although no significant growth suppression was observed by injections of CP (100 mg/kg) at 8-day intervals or those of CP (50 mg/kg) at 4-day intervals, CP injection (100 mg/kg) increased the frequency of tumor peptide-specific T lymphocytes in draining lymph nodes, which was abolished by two injections of CP (50 mg/kg) at a 4-day interval. Alternatively, injection of GEM (50 mg/kg) was superior to that of GEM (100 mg/kg) in suppressing tumor growth in vivo, despite the smaller dose. When CT26-bearing mice were treated with low-dose (50 mg/kg) CP plus (50 mg/kg) GEM at 8-day intervals, tumor growth was suppressed without impairing T cell function; the effect was mainly T cell dependent. The metronomic combination chemotherapy cured one-third of CT26-bearing mice that acquired tumor-specific T cell immunity. The combination therapy decreased Foxp3 and arginase-1 mRNA levels but increased IFN-γ mRNA expression in tumor tissues. The percentages of tumor-infiltrating CD45(+) cells, especially Gr-1(high) CD11b(+) MDSCs, were decreased. These results indicate that metronomic chemotherapy with low-dose CP plus GEM is a promising protocol to mitigate totally Treg- and MDSC-mediated immunosuppression and elicit anti-tumor T cell immunity in vivo.
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