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