Producción CyT

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

Congreso

Autoría:

Maria Belen Bordignon ; PESCE VIGLIETTI, AYELÉN IVANA ; Estefania Paula Juliá ; Pablo Mandó ; Luciana Sabatini ; Jose Mordoh ; Leonardo Fainboim ; Estrella Mariel Levy

Fecha:

2021

Editorial y Lugar de Edición:

Buenos Aires

Resumen *

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 (<0,0001) and CD85j (<0,0001), and lower levels of NKp30 (<0,0001), CD161 (<0,0001) and CD16 (p<001) compared to NKc cells (paired t-tests),which is consistent with previous observations in HD. We then, compared the production of IFNγ by NKc and NKa cells. When PBMC were cultured with SKBR3 HER-2+ cells treated withTRZ, NKa cells from BC patients and HD exhibited increased IFNγ production compared to NKc cells (p<0.01, paired t-test).Conclusions: NKa cells have different immunophenotypic characteristics than NKc cells in BC. Ex vivo treatment of PBMC with TRZ reveals superior effector functions of NKa cells. Our results encouragestudying NKa cells as a potential candidate for predicting Ab-based therapy outcomes in HER2+ BC. Información suministrada por el agente en SIGEVA

Palabras Clave

NK CELLSHER2+ SUBTYPEBREAST CANCER