INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
Medroxiprogesterone acetate drives expansion of CD11b+Gr1high myeloid-derived suppressor cells which suppress NK cell effector functions in tumor-bearing mice
Autor/es:
SPALLANZANI, RAÚL GERMÁN; DALOTTO-MORENO, TOMÁS; ROSSI, LUCAS EZEQUIEL; ÁVILA, DAMIÁN EZEQUIEL; ZIBLAT, ANDREA; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; RABINOVICH, GABRIEL ADRIÁN; SALATINO, MARIANA; ZWIRNER, NORBERTO WALTER
Lugar:
Honolulu
Reunión:
Congreso; Immunology 2013 (100th Congress of the American Association of Immunologists); 2013
Institución organizadora:
The American Association of Immunologists
Resumen:
Hormone
replacement therapy with the progesterone analogue medroxyprogesterone acetate
(MPA) is widely used in postmenopausal women for the treatment of endometrial conditions,
and as a contraceptive. However, prolonged administration of MPA is associated
with increased incidence of breast cancer through ill-defined mechanisms. Our
aim was to explore if MPA threats immunosurveillance to tumors by affecting myeloid-derived
suppressor (MDSCs; CD11b+Gr1+) and NK cells in mammary
tumor-bearing mice. We used the highly metastatic 4T1 breast tumor which does
not express classical progesterone or glucocorticoid receptors. MPA did not
affect primary tumor growth in 4T1-tumor bearing mice but promoted lung
metastasis burden. This effect was accompanied by expansion of splenic CD11b+Gr1+
cells (mostly CD11b+Gr1high cells). Sorted CD11b+Gr1+
cells from MPA-treated tumor bearing mice showed a more pronounced inhibitory
activity of NK cell degranulation in response to YAC-1 cells and IFN-g production in response to cytokines than those
isolated from untreated tumor-bearing mice. Also, MPA significantly increased
the percentage of spleen NK cells in tumor-bearing mice with similar lung infiltration
of CD11b+Gr1+ and NK cells as compared to untreated
tumor-bearing mice. We conclude that in breast cancer-bearing hosts MPA
promotes the accumulation of CD11b+Gr1+ which suppress
NK-cell mediated anti-tumor activity potentially contributing to tumor
progression and metastasis.