CHOLINERGIC SYSTEM AS AN AUTOCRINE-PARACRINE DENDRITIC CELL MODULATOR: RELEVANCE IN THE PATHOGENESIS OF BRAIN TUMORS

INFANTE A, ; GONZÁLEZ N, ; CORONEL JV, ; ITURRIZAGA J, ; RABADÁN A, ; JANCIC C; CRUZ J, ; VERMEULEN M, ; CANDOLFI M ; SALAMONE GV.

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

Cholinergic system as an autocrine-paracrine dendritic cell modulator: relevance in the pathogenesis of brain tumorsA. Infante-Cruz 1, N. González 4, V. Coronel 1, J. Iturrizaga 1,2, C. Jancic 1,3, M. Vermeulen 1,3, M. Candolfi 4; G. Salamone 1,31 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. 4 Instituto de Investigaciones Biomédicas (INBIOMED UBA-CONICET), Facultad de Medicina, UBA.Background: Glioblastoma multiforme (GBM) is the deadliest and most common type of human primary brain tumor. Acetylcholine is a neurotransmitter which can also modulate cell survival, proliferation, and differentiation in neuronal and non-neuronal cells such as immune cells, which has been referred to as a ?non-neuronal cholinergic system?. Objective: This work aimed to elucidate the cholinergic system relevance in the interaction between dendritic and GBM cells and its relationship with the pathology. Materials and Methods: human U251 and U373 cell lines were co-cultured with human dendritic cells (DC) in the presence of cholinergic agonists (10-8M of carbachol/24h), then, we analyze DC activation markers expression by flow cytometry like CD86 and HLA-DR. On the other hand, using datasets from The Cancer Genome Atlas (GBM collections) we analyze the influence of the expression of muscarinic receptors on the immune infiltrate of patients with GBM. Results: Cholinergic system increase the expression of CD86 and HLA-DR in DC co-cultured with U251 or U373 cell line (p