192P - A new neuroendocrine model and in vitro effect of melatonin and serotonin on the PD-L1 ligand and its immunomodulatory action

Background

Lung cancer is a disease that ranks among the first in incidence and mortality in Mexico and worldwide. Neuroendocrine tumors (NETs) have been studied for their neurological and endocrine characteristics; NETs are characterized by having active autocrine/paracrine communication with the microenvironment. Serotonin is precursor of melatonin, an indolamine that can exert immunomodulatory effects and is considered one of the molecules of the neuro-immuno-endocrine axis. The transmembrane protein death ligand 1 (PD-L1) is overexpressed in some types of cancer cells, giving them the ability to camouflage themselves against the immune system. The activation PD-1/PD-L1 are responsible for the proliferation, activation, and cytotoxic secretion of T cells in cancer to generate the antitumor immune response.

Methods

In this work neuroendocrine A549 cells were obtained by two different transdifferentiation methodologies for 72 hours with cAMP inducers in DMEM with 2% fetal bovine serum (NED2%) and without fetal bovine serum (NEDsSFB). This differentiation was corroborated through the evaluation of morphology by light microscopy and the expression of specific markers Chromogranin (CgA) and Synaptophysin (Syn) by rt-PCR. The expression of PD-L1 was assessed in A549 cells, NED2% and NEDsSFB groups by rt-PCR and flow cytometry. A co-culture was performed with the neuroendocrine models with T lymphocytes to observe the cytotoxic effect for 24 hours.

Results

The results showed a new neuroendocrine model, suggest an inhibitory effect in proliferation of melatonin and serotonin from concentrations of 2.5 mM and 0.5 μM respectively in both neuroendocrine models at 24 and 48 hours. It is confirmed for the first time the presence of PD-L1 in the neuroendocrine phenotypes cells of A549 (NED2% and NEDsSFB) and thus a mechanism for evasion of the immune system can be proposed.

Conclusions

We conclude with the development of a new neuroendocrine model as well as the possible mechanism of the decrease in the cytotoxic effect of T lymphocytes in neuroendocrine models.

Legal entity responsible for the study

Universidad Autónoma de Querétaro.

Funding

Universidad Autónoma de Querétaro Conahcyt.

Disclosure

All authors have declared no conflicts of interest.