CHARACTERIZATION OF EO771-TUMOR AS IN VIVO MODEL TO STUDY BREAST CANCER CELL? IMMUNE SYSTEM INTERACTIONS

PAULA A. AGUIRRE; ROBERTO P. MEISS; EVA WERTHEIMER; ANDREA E. ERRASTI; ANTONIO CARRERA-SILVA; LILIAN F. CASTILLO; OMAR A. COSO; MARINA SIMIAN; MANUEL DE LA MATA; MARCOS D. PALAVECCINO; SANTIAGO RODRIGUEZ-SEGUÍ; EDITH C. KORDON.; ALBANA GATTELLI; JUAN P. FEDEDA

Congreso; SAIB SAMIGE 2020; 2020

Breast cancer is the leading cause of cancer death in women worldwide (Global Health Estimates,WHO 2013). The main factor preventing improvements in mortality rates in triple negative (ER- PRHER2-) tumors subtype is the lack of specific treatments due to the absence of therapeutic targets. Furthermore, it was recently observed that breast tumors also rely on immune evasion for their development (Gil Del Alcazar et al, 2017).The anti-tumoral response mediated by T-cells is deficient due to tolerance mechanisms triggered by the tumor itself (DuPage et al, 2011; Willimsky & Blankenstein, 2005). The T cell surface receptorProgrammed death-1 (PD-1) acts as an immune checkpoint and regulates T cell exhaustion. Binding of PD-1 to its ligand, programmed death-ligand 1 (PD-L1), activates downstream signaling pathways and inhibits T cell activation. Moreover, abnormally high PD-L1 expression on tumor cells and antigenpresenting cells in the tumor microenvironment mediates tumor immune escape (Jiang et al, 2019).PD-L1 antibody therapy is successful in several tumor types like melanoma, NSCLC, hepatocellularcarcinoma, gastric cancer but triple negative breast cancer (TNBC) (Sun et al, 2018). Currently, thestrategy in theses case is to run a combination of other target?s drugs along with PD-L1 therapy.Tumor-associated macrophages (TAMs) are relevant cells of the tumor microenvironment, being the M2 subtypes the ones associated with tumor progression. Understanding the dynamics of the myeloid cell population during tumor growth will allow to develop more efficient therapies for TNBC treatment.Mouse model systems have been key in understanding mechanisms underpinning breast cancerdevelopment and delivering new therapies. Among them, the EO771 triple negative-like cell line isemerging as a new spontaneous model to study breast cancer in the C57BL/6 mice background.Our main goal is to validate the EO771 cell as a TBNC model that mimics the shift in the immuneprofile observed in patients. For this purpose, we study the immune population dynamics in TNBC in two stages of tumor progression (early vs. late) by flow cytometry, and generated PD-L1 knockout cell lines using CRISPR/Cas9 technologies.