TY - JOUR

T1 - New Insight into the Role of AhR in Lung Carcinogenesis

AU - Akhmetova, Dinara A.

AU - Kozlov, Vadim V.

AU - Gulyaeva, Ludmila F.

N1 - Funding Information: This work was financially supported by the Russian Science Foundation (grant no. 22-15-00065, “Search for new targets for the diagnosis and therapy of squamous cell lung cancer”). Publisher Copyright: © 2022, The Author(s).

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

KW - AhR

KW - benzo[a]pyrene

KW - cigarette smoke

KW - lung cancer

KW - PD-1

KW - PD-L1

UR - http://www.scopus.com/inward/record.url?scp=85142151358&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/7eeaa9aa-a0e6-365c-b157-073706251e8d/

U2 - 10.1134/S0006297922110013

DO - 10.1134/S0006297922110013

M3 - Review article

C2 - 36509717

AN - SCOPUS:85142151358

VL - 87

SP - 1219

EP - 1225

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 11

ER -