THE ACTIVATION OF THE IMMUNE SYSTEM AS A CONSEQUENCE OF TISSUE REMODELING AFTER ENDOCRINE TREATMENT MAY PARTICIPATE PREVENTING TUMOR RELAPSE

SAHORES, ANA; POLO, LAURA; LAMB, CAROLINE A.; SEQUEIRA, GONZALO; VANZULLI, SILVIA; NOVARO, VIRGINIA; LANARI, CLAUDIA; DALOTTO-MORENO, TOMÁS; RADISKY, DEREK; SALATINO, MARIANA

Buenos Aires

Congreso; Sociedad Argentina de Investigación Clínica; 2017

The role of the immune system during endocrine treatment of mammary carcinomas (MC) has been poorly investigated. We have shown that mifepristone (MFP, antiprogestin) may induce the regression of murine MC that express hormone receptors. Our aim was to characterize the infiltrating cells in MFP-treated MC and evaluate the role of the immune system in antiprogestin-induced tumor regression. Bone marrow (BM) cells from BALB/c-GFP+ mice were iv inoculated into NSG mice to establish the NSG/BM-GFP+ mouse model. 59-2HI tumors, originated in BALB/c mice, were inoculated into NSG or NSG/BM-GFP+ female mice. MFP pellets were implanted sc. when the tumors reached 50 mm2. Tumors were excised after 6 days and cells analyzed by flow cytometry. An increase in T lymphocytes (CD8+; p˂0.01), macrophages (CD11b+ F480+; p˂0.01), NKs cells (p˂0.05), central memory (CD62L+; CCR7+) CD8+ (p˂0.05) and CD4+ (p˂0.001), and effector memory (CD62L-; CCR7- cells) CD8+ (p˂0.05) and CD4+ (p˂0.05) T cells was detected. Conversely, a decrease in the Treg subpopulation (CD4+ CD25+ Foxp3+; p˂0.05), was observed in MFP-treated tumors as compared with control tumors. We also carried out re-challenge assays. MFP pellets were removed after 6 days and tumors excised. Animals were re-inoculated with the same tumor in the opposite flank 5 days after surgery. Sham operated animals were used as controls. Re-challenged NSG/ BM-GFP+ mice had a significant lower tumor take: sham vs. MFP (p˂0.001); control vs MFP (p˂0.01). These data are in agreement with an adaptive immune response elicited during endocrine tumor regression. Regressing tumors may expose intracellular antigens that could be generating a protective immune memory response that might be related with the long free relapse survival induced by endocrine therapy. The characterization of the type of cell death involved, DAMPs exposure and cytokines present in the tumor microenvironment after MFP treatment is being investigated.