REVIEW: New Insight into the Role of AhR in Lung Carcinogenesis

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Dinara A. Akhmetova^1,a*, Vadim V. Kozlov^2,3, and Ludmila F. Gulyaeva^1,2

¹Novosibirsk National Research State University, 630090 Novosibirsk, Russia

²Research Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Siberian Branch of the Russian Academy of Sciences, 630117 Novosibirsk, Russia

³Department of Thoracic Oncology № 3, Novosibirsk Regional Clinical Oncology Center, 630108 Novosibirsk, Russia

^* To whom correspondence should be addressed.

Received June 24, 2022; Revised September 6, 2022; Accepted September 13, 2022

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Lung cancer (LC), one of the most common malignant neoplasms, is the leading cause of high cancer mortality worldwide. Smoking is a risk factor for almost all histological types of LC. Benzo[a]pyrene (BaP), one of the main constituents of tobacco smoke, can cause cancer. It has been established that its toxic effects can develop in the following ways: genotoxic (formation of adducts with DNA) and non-genotoxic or epigenetic. The latter is less known, although it is known that BaP activates aryl hydrocarbon receptor (AhR), which regulate transcription of many target genes, including microRNAs, which can lead to initiation and enhancement of the malignant cell transformation. Recent studies are evaluating the role of AhR in the regulation of immune checkpoints, as cigarette smoke and BaP induce the AhR-regulated expression of PD-L1 (CD274) in lung epithelial cells in vitro and in vivo. In addition, kynurenine (a metabolite of tryptophan) has been found to stimulate the PD-1 (CD279) expression in cytotoxic T cells by activating AhR. Recent studies confirm great importance of AhR expressed in malignant cells for suppression of antitumor immunity. All this makes us rethink the role of AhR in lung carcinogenesis and investigate the mechanisms of its activation by exogenous and endogenous ligands. This review highlights the current understanding of the functional features of AhR and its role in the LC pathogenesis.

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KEY WORDS: lung cancer, AhR, cigarette smoke, benzo[a]pyrene, PD-1, PD-L1

DOI: 10.1134/S0006297922110013

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