ArticleJCI insight2023
Reactive myelopoiesis and FX-expressing macrophages triggered by chemotherapy promote cancer lung metastasis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 14 citations in OpenAlex.
- Tumor-derived stearic acid induces macrophage Egr2 signaling to suppress anti-tumor immunity in breast cancer.bioRxiv : the preprint server for biology · 2026Article
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments.International journal of molecular sciences · 2026Review
- Chemotherapy-induced reactive myelopoiesis promotes expansion of immunosuppressive neutrophil-like monocytes in mice and humans.JCI insight · 2026Article
- Mechanism of Qiling Fuzheng Qingjie granules in alleviating doxorubicin-induced T cell immune dysfunction via mitochondrial energy metabolism.Chinese medicine · 2026Article
- Macrophages in post-chemoradiotherapy hematopoietic injury: a double-edged sword.Cell communication and signaling : CCS · 2026Review
- The CCL2-CCR2 axis in primary lung cancer and pulmonary metastasis: from molecular mechanisms to therapeutic potentials.Frontiers in immunology · 2026Review
- Machine learning analysis of coagulation-related genes for breast cancer diagnosis and prognosis prediction.Scientific reports · 2025Article
- Coagulation proteases modulate nucleic acid uptake and cGAS-STING-IFN induction in the tumor microenvironment.JCI insight · 2025Article
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- The food effect on the pharmacokinetics of TQB3616 capsule in Chinse healthy subjects: a randomized, open-label, single-center, two-period, two-sequence crossover phase I clinical trial.Frontiers in pharmacology · 2025Article
- Cancer treatments as paradoxical catalysts of tumor awakening in the lung.Cancer metastasis reviews · 2024Review
- Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells.Nature reviews. Cancer · 2024Review
- Macrophage diversity in cancer dissemination and metastasis.Cellular & molecular immunology · 2024Review
- A Review of the Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Nonhematologic Malignancies.Diagnostics (Basel, Switzerland) · 2024Review
- Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy.Molecular cancer · 2024Review
- The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer.Cancer medicine · 2024Review
- Adoptive cellular therapy prevents reconstitution of myeloid-derived suppressor cells in the glioma tumor microenvironment.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Several preclinical studies have demonstrated that certain cytotoxic drugs enhance metastasis, but the importance of host responses triggered by chemotherapy in regulating cancer metastasis has not been fully explored. Here, we showed that multidose gemcitabine (GEM) treatment promoted breast cancer lung metastasis in a transgenic spontaneous breast cancer model. GEM treatment significantly increased accumulation of CCR2+ macrophages and monocytes in the lungs of tumor-bearing as well as tumor-free mice. These changes were largely caused by chemotherapy-induced reactive myelopoiesis biased toward monocyte development. Mechanistically, enhanced production of mitochondrial ROS was observed in GEM-treated BM Lin-Sca1+c-Kit+ cells and monocytes. Treatment with the mitochondria targeted antioxidant abrogated GEM-induced hyperdifferentiation of BM progenitors. In addition, GEM treatment induced upregulation of host cell-derived CCL2, and knockout of CCR2 signaling abrogated the pro-metastatic host response induced by chemotherapy. Furthermore, chemotherapy treatment resulted in the upregulation of coagulation factor X (FX) in lung interstitial macrophages. Targeting activated FX (FXa) using FXa inhibitor or F10 gene knockdown reduced the pro-metastatic effect of chemotherapy. Together, these studies suggest a potentially novel mechanism for chemotherapy-induced metastasis via the host response-induced accumulation of monocytes/macrophages and interplay between coagulation and inflammation in the lungs.
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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.