Cholinergic system as an autocrine-paracrine dendritic cell modulator: relevamce in the pathogenesis of brain tumors

INFANTE, ALEJANDRA; GONZALES, NAZARENO; CORONEL, JUAN VALENTIN; ITURRIZAGA, JUAN; RABADAN, ALEJANDRA T; JANCIC, CAROLINA C.; CRUZ, JULIÁN; VERMEULEN, MÓNICA; CANDOLFI, MARIANELA; SALAMONE, GABRIELA VERÓNICA

Congreso; Reunión de Sociedades de Biociencias 2020; 2020

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). We then analysed DC activation marker expression by flow cytometry based on CD86 and HLA-DR. On the other hand, using datasets from The Cancer Genome Atlas (GBM and LGG collections) we analysed the influence of the expression of muscarinic receptors on the immune infiltrate of patients with GBM. Results: Cholinergic system increased the expression of CD86 and HLA-DR in DC co-cultured with U251 or U373 cell line, also, the immune infiltrate analysis showed that the expression of muscarinic receptors such as CHRM1, CHRM2 and CHRM4 are associated with the presence of DCs in GBM and LGG in a significative way. Conclusion: Our findings suggest that the non-neuronal cholinergic system is present in GBM cells and could modulate their crosstalk with the immune system, influencing the survival of patients with LGG and GBM.