ADAPTIVE NATURAL KILLER (NKA) CELLS FACILITATE EFFECTOR FUNCTIONS OF TRASTUZUMAB IN BREAST CANCER (BC)

MARIA BELEN BORDIGNON; AYELÉN IVANA PESCE VIGLIETTI; ESTEFANIA PAULA JULIÁ; PABLO MANDÓ; LUCIANA SABATINI; JOSE MORDOH; LEONARDO FAINBOIM; ESTRELLA MARIEL LEVY

Congreso; Reunión Anula de Sociedades de Biociencias; 2021

NK cells have been regarded as primary effectors of innate immunity, but emerging evidence suggests that a subset of these cells have adaptive immune features, including memory-like properties, such as long-term persistence, robust preferential expansion in response to viral infection, and enhanced antibody-dependent effector functions. Adaptive NK cell subsets are characterized by a lack of FcƐRIγ expression and/or high expression of NKG2C.Objective: To identify adaptive NK cell subpopulations in BC patients and characterize subsets that support robust ex vivo anti-BC activity via trastuzumab (TRZ)- mediated ADCC.With this aim, we analyzed the immunophenotype of NK cells in peripheral blood samples from our cohort of 60 BC patients and 32 healthy donors (HD), both 85% seropositive for human cytomegalovirus. Defining adaptive (NKa) and conventional NK (NKc) cells as FcRγ- and FcRγ+, respectively, NKa subpopulation was detected in 66% of BC patients and 75% of HD. We characterized differential expression of NK-cell inhibitory and activating receptors. NKa cells expressed significantly higher levels of NKG2C (