Extracellular vesicles (EVs), including exosomes and microvesicles, together with apoptotic bodies form a diverse group of nanoparticles that play a crucial role in intercellular communication, participate in numerous physiological and pathological processes. In the context of cancer, they can allow the transfer of bioactive molecules and genetic material between cancer cells and the surrounding stromal cells, thus promoting such processes as angiogenesis, metastasis, and immune evasion. In this article, we review recent advances in understanding how EVs, especially exosomes, influence tumor progression and modulation of the microenvironment. The key mechanisms include exosomes inducing the epithelial–mesenchymal transition, polarizing macrophages toward protumoral phenotypes, and suppressing antitumor immunity. The therapeutic potential of engineered exosomes is highlighted, including their loading with drugs, RNA therapeutics, or tumor antigens to alter the tumor microenvironment. Current techniques for their isolation, characterization, and engineering are discussed. Ongoing challenges include improving exosome loading efficiency, optimizing biodistribution, and enhancing selective cell targeting. Overall, exosomes present promising opportunities to understand tumorigenesis and develop more targeted diagnostic and therapeutic strategies by exploiting the natural intercellular communication networks in tumors. In the context of oncology, regulatory therapy provides the possibility of reproducing the original conditions that are unfavorable for the existence of the cancer process and may thus be a feasible alternative to population treatments. We also review current access to the technology enabling regulatory intervention in the cancer process using exosomes.

The aryl hydrocarbon receptor (AHR) regulates skin responses to microbial, therapeutic, and pollutant ligands. While AHR activation has been linked to both the etiology and treatment of skin diseases, the comparative effects of distinct ligand classes remain understudied. Here we evaluated systemic and cutaneous effects of different AHR ligands applied topically for 28 days. C57BL/6J mice were treated with microbiota-derived indole-3-pyruvic acid (IPY 1%), indole-3-aldehyde (IAld 0.01%), therapeutic, tapinarof (TAP 1%), and pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD 0.000003% (high) or 0.0000003% (low)] or diesel exhaust particle (DEP 0.1%). Systemic effects, skin condition and atopic dermatitis- and chloracne-like outcomes were assessed. Only high-dose TCDD resulted in minor systemic effects including early signs of hepatic injury. While DEP worsened the overall skin condition index, transepidermal water loss, ear thickness, scratching and grooming were unchanged for all chemicals. Both TAP and high-dose TCDD elevated desquamation and produced chloracne-like pathology characterized by hyperkeratosis, sebaceous gland involution and cyst-formation. TCDD caused epidermal atrophy, whereas TAP caused epidermal hyperplasia, infundibular dilatation and extended hyperkeratosis. TAP and high-dose TCDD were equally effective in increasing Cyp1a1 and Cyp1b1 mRNA, yet TAP preferentially increased Nrf2 targets, Epgn, Sprr2d, and Slpi, previously reported to drive a chloracne-like response in mice. Human keratinocytes showed similar preferential induction of EPGN and SPRR2D by TAP. These findings highlight AHR activator-specific skin effects, in part, associated with differences in selective ligand activation of modifying signaling pathways.