CD11b+Ly6G+Ly6Cint myeloid-derived suppressor cells become expanded by medroxiprogesterone acetate in mammary tumor bearing hosts and suppress NK cell effector functions.

Abstract

Event Abstract Back to Event CD11b+Ly6G+Ly6Cint myeloid-derived suppressor cells become expanded by medroxiprogesterone acetate in mammary tumor bearing hosts and suppress NK cell effector functions. Raul G. Spallanzani1*, Tomas Dalotto Moreno1, Damian E. Avila1, Andrea Ziblat1, Carolina I. Domaica1, Mercedes B. Fuertes1, Ximena L. Raffo Iraolagoitia1, Gabriel A. Rabinovich1, Mariana Salatino1 and Norberto W. Zwirner1* 1 Instituto de Biologia y Medicina Experimental, Argentina The progesterone analogue medroxyprogesterone acetate (MPA) is being widely used in postmenopausal women, for the treatment of endometrial conditions, and as a contraceptive. However, hormone replacement therapy in postmenopausal women has been associated with increased incidence of breast cancer through ill-defined mechanisms. In this work, we explored whether prolonged exposure to MPA restrains immunosurveillance to tumors through mechanisms involving myeloid-derived suppressor cells (MDSCs; CD11b+Gr1+, composed by CD11b+Ly6G+Ly6Cint and CD11b+Ly6G-Ly6Chigh) and NK cells in mammary tumor-bearing mice. Using the highly metastatic 4T1 breast tumor (which does not express the classical progesterone receptor), we observed that MPA did not affect primary tumor growth but induced a preferential expansion of spleen and bone marrow CD11b+Ly6G+Ly6Cint but not CD11b+Ly6G-Ly6Chigh cells. Also, MPA significantly increased the percentage of spleen and lung NK cells in tumor-bearing mice with similar lung infiltration of CD11b+Gr1+ cells as compared to untreated tumor-bearing mice. However, sorted CD11b+Gr1+ cells (comprising more than 90% of CD11b+Ly6G+Ly6Cint cells) from MPA-treated tumor bearing mice displayed a more pronounced suppressive activity on NK cell degranulation in response to YAC-1 cells and a stronger inhibition of IFN-g production of NK cells in response to cytokines than those CD11b+Gr1+ cells isolated from untreated tumor-bearing mice. Thus, in breast cancer-bearing hosts MPA promotes the accumulation of CD11b+Ly6G+Ly6Cint cells which display a suppressive activity on NK-cell effector functions, potentially contributing to tumor progression and metastasis. Keywords: NK cell, myeloid-derived suppressor cells, breast cancer, Medroxiprogesterone Acetate, Citotoxicity Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Spallanzani RG, Dalotto Moreno T, Avila DE, Ziblat A, Domaica CI, Fuertes MB, Raffo Iraolagoitia XL, Rabinovich GA, Salatino M and Zwirner NW (2013). CD11b+Ly6G+Ly6Cint myeloid-derived suppressor cells become expanded by medroxiprogesterone acetate in mammary tumor bearing hosts and suppress NK cell effector functions.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00629 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Raul G Spallanzani, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina, gerspa@gmail.com Dr. Norberto W Zwirner, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina, nzwirner@ibyme.conicet.gov.ar Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Raul G Spallanzani Tomas Dalotto Moreno Damian E Avila Andrea Ziblat Carolina I Domaica Mercedes B Fuertes Ximena L Raffo Iraolagoitia Gabriel A Rabinovich Mariana Salatino Norberto W Zwirner Google Raul G Spallanzani Tomas Dalotto Moreno Damian E Avila Andrea Ziblat Carolina I Domaica Mercedes B Fuertes Ximena L Raffo Iraolagoitia Gabriel A Rabinovich Mariana Salatino Norberto W Zwirner Google Scholar Raul G Spallanzani Tomas Dalotto Moreno Damian E Avila Andrea Ziblat Carolina I Domaica Mercedes B Fuertes Ximena L Raffo Iraolagoitia Gabriel A Rabinovich Mariana Salatino Norberto W Zwirner PubMed Raul G Spallanzani Tomas Dalotto Moreno Damian E Avila Andrea Ziblat Carolina I Domaica Mercedes B Fuertes Ximena L Raffo Iraolagoitia Gabriel A Rabinovich Mariana Salatino Norberto W Zwirner Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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