STUDY OF THE INTERACTION BETWEEN GLIOBLASTOMA DERIVED gd T LYMPHOCYTES AND NEUTROPHILS

ROSATO, MICAELA; SHIROMIZU, CAROLINA M; SALAMONE, GABRIELA V; ROSSO, DAVID A; CORONEL, JUAN V; JANCIC, CAROLINA C; ITURRIZAGA, JUAN; RABADAN, ALEJANDRA T

CABA

Congreso; Reunión anual de Sociedades Bioscientíficas. SAI-SAIC-SAFIS; 2020

SAIC- SAI- SAFIS

STUDY OF THE INERACTION BETWEEN GLIOBLASTOMA DERIVED  T LYMPHOCYTES AND NEUTROPHILSMicaela Rosato1, David A Rosso1, Juan K. Iturrizaga Meza1,2, Carolina M Shiromizu1, Alejandra Teresa Rabadán2, Gabriela Salamone1,3, Carolina C Jancic1,31 Instituto de Medicina Experimental (IMEX) CONICET ? Academia Nacional de Medicina, Buenos Aires, Argentina.2 División Neurocirugía del Instituto de Investigaciones Médicas A Lanari. Universidad de Buenos Aires. Universidad de Buenos Aires.3 Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires. Buenos Aires, Argentina.  T cells constitute a functionally specialized subset of T lymphocytes which act as early sensors of cellular stress and infection.  T cells play a critical role in the recruitment and activation of neutrophils at the sites of inflammation, in addition, neutrophils can regulate  T cell activity. Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. GBM is clinically highly aggressive because of evolutionary dynamics induced by cross talk between cancer cells and a heterogeneous group of immune cells in tumor microenvironment. We have previously reported that neutrophils, obtained from healthy donors, regulate  T cell activation induced by phosphoantigens. Now, we aimed to investigate whether  T cells derived from GBM-bearing patient were susceptible to be modulated by neutrophils. To achieve this purpose,  T cells were purified from human peripheral blood mononuclear cells, by using an anti-TCR  MicroBead isolation kit. Neutrophils were isolated by dextran sedimentation. After purification,  T cells were stimulated or not with (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP: 10 µM, 60 min), and then were cultured with or without neutrophils. After 24 hours, we evaluated the activation of  T cells by analyzing CD69 expression and IFN- and TNF- production by flow cytometry and ELISA, respectively. Our results showed that the response induced by HMBPP on GBM bearing patient-derived  T cells, was reverted in presence of neutrophils. This was demonstrated by a decrease in the expression of CD69 and in the IFN- and TNF- production (p