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

Maciej M. Markiewski, Surya Kumari Vadrevu, Sharad K. Sharma, Navin Kumar Chintala, Shanawaz Ghouse, Jun Hung Cho, David P. Fairlie, Yvonne Paterson, Aristotelis Astreinidis, Magdalena Karbowniczek

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2989-2999
Number of pages11
JournalJournal of Immunology
Volume198
Issue number7
DOIs
StatePublished - Apr 1 2017

Fingerprint

Anaphylatoxin C5a Receptor
Complement C5a
Complement Receptors
Neoplasms
Immunosuppressive Agents
T-Lymphocytes
Immunosuppression
ribosomal protein S19
Breast Neoplasms
Regulatory T-Lymphocytes
Growth and Development
Ovarian Neoplasms

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Markiewski, M. M., Vadrevu, S. K., Sharma, S. K., Chintala, N. K., Ghouse, S., Cho, J. H., ... Karbowniczek, M. (2017). The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1. Journal of Immunology, 198(7), 2989-2999. https://doi.org/10.4049/jimmunol.1602057

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; Astreinidis, Aristotelis; Karbowniczek, Magdalena.

In: Journal of Immunology, Vol. 198, No. 7, 01.04.2017, p. 2989-2999.

Research output: Contribution to journalArticle

Markiewski, MM, Vadrevu, SK, Sharma, SK, Chintala, NK, Ghouse, S, Cho, JH, Fairlie, DP, Paterson, Y, Astreinidis, A & Karbowniczek, M 2017, 'The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1', Journal of Immunology, vol. 198, no. 7, pp. 2989-2999. https://doi.org/10.4049/jimmunol.1602057
Markiewski MM, Vadrevu SK, Sharma SK, Chintala NK, Ghouse S, Cho JH et al. The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1. Journal of Immunology. 2017 Apr 1;198(7):2989-2999. https://doi.org/10.4049/jimmunol.1602057
Markiewski, Maciej M. ; Vadrevu, Surya Kumari ; Sharma, Sharad K. ; Chintala, Navin Kumar ; Ghouse, Shanawaz ; Cho, Jun Hung ; Fairlie, David P. ; Paterson, Yvonne ; Astreinidis, Aristotelis ; Karbowniczek, Magdalena. / The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1. In: Journal of Immunology. 2017 ; Vol. 198, No. 7. pp. 2989-2999.
@article{f41cd97b12b94a6a9e3d39ef66f78682,
title = "The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1",
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.",
author = "Markiewski, {Maciej M.} and Vadrevu, {Surya Kumari} and Sharma, {Sharad K.} and Chintala, {Navin Kumar} and Shanawaz Ghouse and Cho, {Jun Hung} and Fairlie, {David P.} and Yvonne Paterson and Aristotelis Astreinidis and Magdalena Karbowniczek",
year = "2017",
month = "4",
day = "1",
doi = "10.4049/jimmunol.1602057",
language = "English (US)",
volume = "198",
pages = "2989--2999",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1

AU - Markiewski, Maciej M.

AU - Vadrevu, Surya Kumari

AU - Sharma, Sharad K.

AU - Chintala, Navin Kumar

AU - Ghouse, Shanawaz

AU - Cho, Jun Hung

AU - Fairlie, David P.

AU - Paterson, Yvonne

AU - Astreinidis, Aristotelis

AU - Karbowniczek, Magdalena

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85016328881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016328881&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1602057

DO - 10.4049/jimmunol.1602057

M3 - Article

VL - 198

SP - 2989

EP - 2999

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -