Proliferative Effects of Lung Cancer Cells Derived Exosomes on T Cells

HIGHLIGHTS

• The expression of exosomes is higher in cancer environment.

• Exosomes effects T cells proliferation.

• The expression of CD4-IFNγ and CD8-IFNγ are deregulated by lung cancer exosomes.

Abstract

Lung cancer patients have higher expression of Exosomes (EXs) carrying several bioactive molecules including lipids, protein, carbohydrates, and different types of RNAs. Upon delivery of EXs into the recipient cells different behavioral changes are observed in the biological mechanisms of the cell. In the current study, we aimed to compare the EXs production in lung cancer cells (H1975) in two different conditions including normal conditions (NC) (20% O₂, 5% CO2, 10% FBS and 100 U/mL penicillin and 100 μg/mL streptomycin added media with pH 7) and our established conditions (EC) (1% O₂, 5% CO₂ and FBS/antibiotic-free media with pH 6). We also studied the proliferative effects of these EXs (NC and EC) on Jurkat cells (immortalized T lymphocytes) and proliferation of some of the human T cells population was also observed with co-culture experiments. From the Nano sight analysis, a high quantity of EXs was observed in EC as compared with the NC. EXs isolated from both conditions showed proliferative effects on Jurkat cells. Among the human T cells population, EC-EXs were shown low expression of CD8-IFNγ and CD4-IFN γ in comparison with NC-EXs. These results support the hypothesis that Lung cancer cells derived EXs can interact with the T cells mechanisms leading to the low immune response in the cancer microenvironment and providing a favorable condition for cancer cells. Such studies need validation in vivo to verify the actual mechanisms which could be effective in potential therapeutic strategies.

Keywords:
Lung Cancer; Exosomes; T cells proliferation; Interferon-gamma.

GRAPHICAL ABSTRACT