ArticleJournal for immunotherapy of cancer2022
CCR1 and CCR5 mediate cancer-induced myelopoiesis and differentiation of myeloid cells in the tumor.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- GALNT6-glycosylated LRG1 mediates the interaction between M2 macrophages and pancreatic cancer cells by activating CCR1/PI3K/AKT axis.Molecular and cellular biochemistry · 2026Article
- Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy.Journal for immunotherapy of cancer · 2026Article
- Current Approaches and Emerging Strategies in the Treatment of Peritoneal Carcinomatosis.International journal of molecular sciences · 2026Review
- Single-nucleus multimodal spatial transcriptomics reveals spatial colocalization of neoantigen-expressing tumor cells and cognate T cells.Nature biotechnology · 2026Article
- Correlated expression of MYBL2 and CCL5 defines an immunosuppressive microenvironment and predicts poor prognosis in intrahepatic cholangiocarcinoma.BMC cancer · 2026Article
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- CCR1Journal of advanced research · 2026Article
- Article
- Exploring the Potential of Receptor Silencing in the Tumor Microenvironment by RNA Interference.Biomolecules · 2026Review
- CCR5 marks a subset of mouse hematopoietic stem cells that are myeloid primed and expand with age.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis.Biochemistry research international · 2026Article
- Beyond density: mapping the functional landscapes of macrophage-T lymphocyte niches in the tumor microenvironment.Frontiers in immunology · 2026Review
- Beyond the tumor microenvironment: Orchestrating systemic T‑cell response for next‑generation cancer immunotherapy (Review).International journal of oncology · 2025Review
- Trained immunity in chronic inflammatory diseases and cancer.Nature reviews. Immunology · 2025Review
- Harnessing myeloid cells in cancer.Molecular cancer · 2025Review
- Bridging inflammation and proliferation: scRNA-seq analysis of chemotactic and growth factor signaling in mouse skin wound repair.Frontiers in immunology · 2025Article
- Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial.Nature cancer · 2024Article
- SLAMF8 can predict prognosis of pan-cancer and the immunotherapy response effectivity of gastric cancer.Aging · 2024Article
- The Tumor Immune Microenvironment Architecture Correlates with Risk of Recurrence in Head and Neck Squamous Cell Carcinoma.Cancer research · 2023Article
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCancer-induced 'emergency' myelopoiesis plays a key role in tumor progression by inducing the accumulation of myeloid cells with a suppressive phenotype peripherally and in the tumor. Chemokine receptors (CCRs) and, in particular, CCR1, CCR2, CCR5, and CCR7 are emerging as key regulators of myeloid cell trafficking and function but their precise role has not been completely clarified yet because of the signal redundancy, integration, and promiscuity of chemokines and of the expression of these CCRs on other leukocyte subsets.
methodsWe used the 4PD nanoparticle for the in vivo targeted silencing of CCR1, CCR2, CCR5, and/or CCR7 in the myeloid cells of tumor bearing mice to evaluate the effect of treatments on tumor growth, myeloid cell trafficking and polarization. We used flow and image cytometry and functional assays to monitor changes in the tumor microenvironment and depletion experiments and immune deficient mice to determine the role of Ly6G
results4PD-mediated in vivo silencing of CCR1 and CCR5 on myeloid cells and myeloid precursors was necessary and sufficient to inhibit tumor progression. Functional studies indicated that this antitumor effect was not mediated by alteration of myeloid cell chemotaxes but rather by the repolarization of polymorphonuclear myeloid-derived suppressor cells (MDSCs) into tumoricidal neutrophils. Transcriptome functional and cytokine analysis indicated that tumor derived factors induced CCL3 and CCL4 in HSPCs that, through the autocrine engagement of CCR1 and CCR5, induced HSPCs differentiation in MDSCs. These finding were confirmed across mice with different genetic backgrounds and using HSPCs from umbilical cord blood and peripheral blood of patients with cancer.
conclusionsOur data support the notion that CCR1 and CCR5 and their ligands are a master immunological hub activated by several tumor derived factors. Activation of this pathway is necessary for the differentiation of MDSCs and protumoral macrophages.
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