Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities

Table 1 Aryl hydrocarbon receptor signaling and its impact on

Aspect of ESCC	Impact of AhR activation	Mechanism	Ref.
Carcinogenesis
Proliferation	Increased	Upregulates cyclin D1, downregulates p21	[31,33]
Apoptosis	Inhibited	Upregulates anti-apoptotic factors like Bcl-2	[34]
DNA repair	Impaired	Downregulates expression of key DNA repair enzymes	[36]
Metabolic reprogramming	Promotes Warburg effect	Increases reliance on aerobic glycolysis	[28]
Stemness	Enhanced	Promotes self-renewal and differentiation of cancer stem cells	[37,38]
EMT	Induced	Upregulates EMT-inducing transcription factors like Twist1 and Snail	[41,43]
Immune escape
T cell function	Suppressed	Inhibits proliferation and cytokine production of CD8+ CTLs, promotes differentiation of Tregs	[45,46]
Myeloid cell recruitment	Increased	Promotes recruitment and expansion of MDSCs	[47]
Immune checkpoint regulation	Potential upregulation of PD-L1 expression	May contribute to immune escape by inhibiting T cell activity	[49]

AhR: Aryl hydrocarbon receptor; Bcl-2: B-cell lymphoma 2; CD8+ CTLs: CD8+ Cytotoxic T lymphocytes; EMT: Epithelial-mesenchymal transition; ESCC: Esophageal squamous cell carcinoma; MDSCs: Myeloid-derived suppressor cells; PD-L1: Programmed death-ligand 1; Snail: Zinc finger protein SNAI1; Twist1: Twist family BHLH Transcription factor 1; Tregs: Regulatory T cells.