MICROVESICLES FROM GLIOBLASTOMA CELL LINE ACTÍVATE  T LYMPHOCYTES

ROSATO MICAELA, ; ROSSO DAVID ANTONIO, ; KEITELMAN IRENE, ; SHIROMIZU CAROLINA MAIUMI, ; SABBIONE FLORENCIA, ; CORONEL JUAN VALENTÍN, ; INFANTE CRUZ ALEJANDRA, ; TREVANI ANALÍA SILVINA, ; SALAMONE GABRIELA V, ; JANCIC, CAROLINA C

Congreso; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; 2021

MICROVESICLES FROM GLIOBLASTOMA CELL LINE ACTIVATE GAMMA DELTA T LYMPHOCYTESGlioblastoma multiforme (GBM) is the most aggressive malignant type of cerebral tumor in adults and has a median survival of less than a year after diagnosis. GBM is refractory to standard treatments such as gross total resection, followed by radiotherapy and chemotherapy because of its infiltration nature. Therefore, current therapies are only a temporary and limited solution. However, there are new immunotherapy approaches to GBM and one of them involves the adoptive transfer of γδ T cells. This subset of T lymphocytes expresses a restricted repertoire and can recognize stressed and malignant cells, and induce their apoptosis. Within the peripheral blood γδ T cells, those that express TCRVγ9Vδ2 chains constitute the main subsets of γδ T cells in a healthy human. We recently demonstrated that soluble factors released by GBM cells activate γδ T lymphocytes by inducing a Th1-like profile. Moreover, it is well known that tumor cells can secrete extracellular vesicles, among them, microvesicles (MV), which contain molecules that regulate tumor microenvironment to allow their growth and progression. For those reasons, in this work we aimed to evaluate whether MV, as released factors derived from human GBM cell line U373, were involved in the modulation of γδ T lymphocytes? functionality. For this purpose, γδ T cells were purified from human peripheral blood mononuclear cells, by using an anti-TCR γδ MicroBead isolation kit. After purification, γδ T cells were incubated for 24 hours with MV obtained from U373 cell line by differential centrifugation. After incubation, we analyzed the activation state of γδ T cells by measuring the expression of CD69 by flow cytometry, and TNF-α by ELISA. Our results indicated that MV induced an increase in the expression of CD69 (p