Regulation of immune checkpoints by electronic cigarette

An e-cigarette device consists of a cartridge that stores e-liquid, a mouthpiece, a heating element, and a power source. The e-liquid is heated by a coil and a wick, generating an aerosol that is inhaled by the user. Although some sectors promote e-cigarettes as a smoking cessation tool, increasing scientific evidence associates their use with adverse health effects, including cytotoxic, genotoxic, potentially carcinogenic effects, and immunological alterations. Immune checkpoints are a group of molecules with co-stimulatory or co-inhibitory functions that bind their ligands to activate or suppress intracellular signaling pathways in T cells. Inhibitory immune checkpoints are expressed on immune cells and regulate the magnitude of immune activation to prevent excessive immune responses. Several studies have reviewed the effects of cigarette smoke and its components on immune checkpoints; however, the effects of e-liquids and their aerosols on immune checkpoints have not been comprehensively reviewed. In this work, we aimed to analyze and discuss the contribution of e-cigarette aerosols and core e-liquid components to the regulation of inhibitory immune checkpoint expression and function, as well as their biological impact on cellular processes. Available evidence indicates that e-cigarette aerosols and major e-liquid constituents can modulate the expression and function of diverse inhibitory immune checkpoints in models of various cancers, rheumatoid arthritis, and physical stress. Further studies are required to clarify the biological consequences of immune checkpoint alterations induced by e-cigarette aerosols and their contribution to disease development.