The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1

Markiewski, Maciej M., Vadrevu, Surya Kumari, Sharma, Sharad K., Chintala, Navin Kumar, Ghouse, Shanawaz, Cho, Jun-Hung, Fairlie, David P., Paterson, Yvonne, Astrinidis, Aristotelis and Karbowniczek, Magdalena (2017) The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1. Journal of Immunology, 198 7: 2989-2999. doi:10.4049/jimmunol.1602057

Author Markiewski, Maciej M.
Vadrevu, Surya Kumari
Sharma, Sharad K.
Chintala, Navin Kumar
Ghouse, Shanawaz
Cho, Jun-Hung
Fairlie, David P.
Paterson, Yvonne
Astrinidis, Aristotelis
Karbowniczek, Magdalena
Title The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
Publication date 2017-04-01
Sub-type Article (original research)
DOI 10.4049/jimmunol.1602057
Open Access Status Not yet assessed
Volume 198
Issue 7
Start page 2989
End page 2999
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Subject 2403 Immunology
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-b, 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1R01CA190209
RP 120168
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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