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Vila-Leahey A, Oldford SA, Marignani PA, et al. Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice. Oncoimmunology. 2016;5(7):e1151591doi: 10.1080/2162402X.2016.1151591.
Vila-Leahey, A., Oldford, S. A., Marignani, P. A., Wang, J., Haidl, I. D., & Marshall, J. S. (2016). Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice. Oncoimmunology, 5(7), e1151591. https://doi.org/10.1080/2162402X.2016.1151591
Vila-Leahey, Ava, et al. "Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice." Oncoimmunology vol. 5,7 (2016): e1151591. doi: https://doi.org/10.1080/2162402X.2016.1151591
Vila-Leahey A, Oldford SA, Marignani PA, Wang J, Haidl ID, Marshall JS. Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice. Oncoimmunology. 2016 Mar 10;5(7):e1151591. doi: 10.1080/2162402X.2016.1151591. eCollection 2016 Jul. PMID: 27622015; PMCID: PMC5006904.
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Oncoimmunology. 2016 Mar 10;5(7):e1151591. doi: 10.1080/2162402X.2016.1151591. eCollection 2016 Jul.

Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice.

Oncoimmunology

Ava Vila-Leahey, Sharon A Oldford, Paola A Marignani, Jun Wang, Ian D Haidl, Jean S Marshall

Affiliations

  1. Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
  2. Department of Biochemistry and Molecular Biology, Dalhousie University , Halifax, Nova Scotia, Canada.
  3. Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; IWK Health Centre, Halifax, Nova Scotia, Canada.

PMID: 27622015 PMCID: PMC5006904 DOI: 10.1080/2162402X.2016.1151591

Abstract

Histamine receptor 2 (H2) antagonists are widely used clinically for the control of gastrointestinal symptoms, but also impact immune function. They have been reported to reduce tumor growth in established colon and lung cancer models. Histamine has also been reported to modify populations of myeloid-derived suppressor cells (MDSCs). We have examined the impact of the widely used H2 antagonist ranitidine, on both myeloid cell populations and tumor development and spread, in three distinct models of breast cancer that highlight different stages of cancer progression. Oral ranitidine treatment significantly decreased the monocytic MDSC population in the spleen and bone marrow both alone and in the context of an orthotopic breast tumor model. H2 antagonists ranitidine and famotidine, but not H1 or H4 antagonists, significantly inhibited lung metastasis in the 4T1 model. In the E0771 model, ranitidine decreased primary tumor growth while omeprazole treatment had no impact on tumor development. Gemcitabine treatment prevented the tumor growth inhibition associated with ranitidine treatment. In keeping with ranitidine-induced changes in myeloid cell populations in non-tumor-bearing mice, ranitidine also delayed the onset of spontaneous tumor development, and decreased the number of tumors that developed in LKB1(-/-)/NIC mice. These results indicate that ranitidine alters monocyte populations associated with MDSC activity, and subsequently impacts breast tumor development and outcome. Ranitidine has potential as an adjuvant therapy or preventative agent in breast cancer and provides a novel and safe approach to the long-term reduction of tumor-associated immune suppression.

Keywords: H2 antagonist; histamine; metastasis; monocytes; myeloid cells; myeloid-derived suppressor cells; tumor immunology

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