The etiology of gallbladder cancer (GBC) is multifactorial, with chronic inflammation resulting from infections, autoimmune diseases, and lifestyle factors playing a pivotal role. Vitamin D deficiency (VDD) has been implicated in the pathogenesis of autoimmune disorders and various malignancies, including GBC. Research on autoimmune diseases highlights the anti-inflammatory properties of vitamin D, suggesting its potential to mitigate disease progression. In oncology, VDD has similarly been linked to increased inflammation, which may contribute to both the initiation and progression of cancer. A critical component in carcinogenesis, as well as in the immunomodulatory effects of vitamin D in autoimmune conditions, is the balance between T-helper 17 (Th17) cells and regulatory T (Treg) cells. We hypothesize that vitamin D may inhibit epithelial-mesenchymal transition (EMT) in GBC by modulating the spatial distribution of tumor-infiltrating T cells, particularly through the regulation of the Th17/Treg balance at the tumor margins. This Th17/Treg imbalance may act as a mechanistic link between VDD and the progression of GBC carcinogenesis. Investigating the role of an Th17/Treg imbalance as a mediator in VDD-induced EMT in GBC not only provides deeper insights into the pathogenesis of GBC but also sheds light on broader mechanisms relevant to the development of other solid organ cancers, given the expanding recognition of the roles of VDD and Th17/Treg cells in cancer biology.
Keywords: T cell; cancer; epithelial–mesenchymal transition; vitamin D.