Abstract
The different immune system cells communicate and coordinate a response using a complex and evolved language of cytokines and chemokines. These cellular interactions carry out multiple functions in distinct cell types with numerous developmental outcomes. Despite the plethora of different cytokines and their cognate receptors, there is a restricted number of signal transducers and activators to control immune responses. Herein, we report on a new class of immunomodulatory signaling molecules based on volatile molecules (VMs, namely, volatile organic compounds [VOCs]), by which they can affect and/or control immune cell behavior and transcriptomic profile without any physical contact with other cells. The study demonstrates the role of VMs by analyzing non-contact cell communication between normal and cancerous lung cells and U937 monocytes, which are key players in the tumor microenvironment. Integrated transcriptome and proteome analyses showed the suggested regulatory role of VMs released from normal and cancer cells on neighboring monocytes in several molecular pathways, including PI3K/AKT, PPAR, and HIF-1. Presented data provide an initial platform for a new class of immunomodulatory molecules that can potentially mirror the genomic and proteomic profile of cells, thereby paving the way toward non-invasive immunomonitoring.