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J Immunol. 2017 Apr 1;198(7):2989-2999. doi: 10.4049/jimmunol.1602057. Epub 2017 Feb 22.

The Ribosomal Protein S19 Suppresses Antitumor Immune Responses via the Complement C5a Receptor 1.

Author information

1
Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601; maciej.markiewski@ttuhsc.edu magdalena.karbowniczek@ttuhsc.edu.
2
Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
3
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
4
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, Queensland 4072, Australia; and.
5
Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Abstract

Relatively little is known about factors that initiate immunosuppression in tumors and act at the interface between tumor cells and host cells. In this article, we report novel immunosuppressive properties of the ribosomal protein S19 (RPS19), which is upregulated in human breast and ovarian cancer cells and released from apoptotic tumor cells, whereupon it interacts with the complement C5a receptor 1 expressed on tumor infiltrating myeloid-derived suppressor cells. This interaction promotes tumor growth by facilitating recruitment of these cells to tumors. RPS19 also induces the production of immunosuppressive cytokines, including TGF-β, by myeloid-derived suppressor cells in tumor-draining lymph nodes, leading to T cell responses skewed toward Th2 phenotypes. RPS19 promotes generation of regulatory T cells while reducing infiltration of CD8+ T cells into tumors. Reducing RPS19 in tumor cells or blocking the C5a receptor 1-RPS19 interaction decreases RPS19-mediated immunosuppression, impairs tumor growth, and delays the development of tumors in a transgenic model of breast cancer. This work provides initial preclinical evidence for targeting RPS19 for anticancer therapy enhancing antitumor T cell responses.

PMID:
28228558
PMCID:
PMC5360500
DOI:
10.4049/jimmunol.1602057
[Indexed for MEDLINE]
Free PMC Article

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