Correlation between aryl hydrocarbon receptor and IL‐17⁺ and Foxp3⁺ T‐cell infiltration in bladder cancer

Abstract

Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3+ regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3+ Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non‐tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3+/CD4+) and Th17 (IL‐17+/CD4+), as well as AHR+ cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3+ Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non‐tumoural tissues. Also, the percentage of AHR+ lymphocytes and AHR+ cells was increased significantly in bladder tumour tissues rather than non‐tumoural tissues. This study also found a relation between AHR and Foxp3+/CD4+ T lymphocytes ratio cells in BC. The percentage of Foxp3+ Tregs and AHR+ cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3+ Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3+Treg in BC can lead to a potential cancer therapeutic possibility.

Establishment of a prognostic model related to tregs and natural killer cells infiltration in bladder cancer

“…According to earlier studies, Tregs inhibit long-lasting immune reactions to viruses, tumors, and self-antigens; the infiltrate tumor tissue and are linked to a bad prognosis in cancer patients; the quantity of Treg was negatively correlated with recurrence-free survival in BUC and substantially increased in peripheral blood and tumor tissue[ 7 ]. The grade and stage of BUC were significantly associated with the proportion of Foxp3+ Tregs[ 8 ]. The most significant component of natural immunity is played by NK cells, which can directly destroy target cells like cancerous or virus-infected ones.…”

AhR may be involved in Th17 cell differentiation in chronic hepatitis B

“…It is made up of the Per‐Arnt‐Sim structure, which associates with a variety of both exogenous and endogenous compounds as well as certain cofactors such as heat shock protein 90 (HSP90) and proteins associated with HBV‐X 43,48 . AhR is essential for mediating the biological response to a range of physiological and environmental chemicals 43,49 . AhR is present in intrinsic and specific immune cells and regulates immune cell proliferation, differentiation and cytokine production, which are important for infection and inflammation control 50,51 …”

“…43,48 AhR is essential for mediating the biological response to a range of physiological and environmental chemicals. 43,49 AhR is present in intrinsic and specific immune cells and regulates immune cell proliferation, differentiation and cytokine production, which are important for infection and inflammation control. 50,51 Recently, it has been discovered that AhR plays an important role in controlling Th17/Treg equilibrium.…”

CD3high and FoxP3− tumor-infiltrating lymphocytes in the invasive margin as a favorable prognostic marker in patients with invasive urothelial carcinoma of the bladder

“…FoxP3 is a transcription factor required by regulatory T cells (Tregs) to maintain immune cell homeostasis and inhibit antitumor immune responses [24]. Although FoxP3 + TILs were shown to predict better survival in head and neck, bladder, and colon cancers [20,25,26], numerous studies suggested that Tregs are immunosuppressive and that their presence/abundance is associated with poor prognosis in patients with cancer [21,27,28]. However, some studies reported TILs as a prognostic marker in bladder cancer [21,22].…”