Role of the immune system in antiprogestin-induced mammary tumor regression.

ANA SAHORES; LAURA POLO; MARIANA SALATINO; GONZALO R. SEQUEIRA; SILVIA VANZULLI; CAROLINE LAMB; TOMAS DALOTTO-MORENO; VIRGINIA NOVARO; CLAUDIA LANARI

Congreso; Reunión anual SAIC-SAI-SAFE; 2016

The role of the immune system in the regression of mammary carcinomas (MC) using endocrine therapies has been poorly investigated. We have shown that mifepristone (MFP, antiprogestin) induces the regression of murine MC that express progesterone receptors regardless of the immune system. Characterization of the immune cells in regressing tumors may provide clues related to their role in the prevention of tumor regrowth. Our aim was to characterize the infiltrating cells in MFP-treated MC and to evaluate whether MFP was able to protect against tumor growth in a tumor re-challenge assay after complete tumor resection. Bone marrow (BM) cells from BALB/c-GFP+ mice were iv inoculated into immunodeficient NSG mice to establish the NSG/BM-GFP+ mouse model. 59-2-HI tumors, originated in BALB/c mice, were inoculated into NSG or NSG/BM-GFP+ female mice. MFP pellets (0.2 mg) were implanted sc when the tumors reached 50 mm2. Tumors were excised after 3 or 6 days and isolated cells analyzed by flow cytometry. An increase in T lymphocytes (CD8+) and in macrophages (CD11b+ F480+; p˂0.01), and a decrease in the Treg subpopulation (CD4+ CD25+ Foxp3+; p˂0.05), was observed in MFP-treated tumors. In the re-challenge assay, tumors were excised and pellets removed 6 days after MFP treatment. Animals were orthotopically re-inoculated with 59-2-HI tumors in the opposite flank 5 days after surgery. Sham operated animals were used as controls. All secondary transplants growing in untreated mice reached 200 mm2 before day 47 while only 50% of those mice previously treated with MFP reached this size, p