Previous studies mainly focused on the role of the epidermal growth factor receptor (EGFR) in tumor cells, whereas the effects of the EGFR on immune responses has not been determined. Our study shows that the EGFR signaling pathway play a role in the regulation of regulatory T cells (Treg cells) in cancer patients. The EGF-like growth factor Amphiregulin (AREG) protein was frequently up-regulated in a tissue microarray, which was associated with worse overall survival. Additionally, in sera, tissue specimens, and effusions of lung or gastric cancer patients, up-regulated AREG protein enhanced the suppressive function of Treg cells. AREG maintained the Treg cell suppressive function via the EGFR/GSK-3β/Foxp3 axis in vitro and in vivo. Furthermore, inhibition of EGFR by the tyrosine kinase inhibitor gefitinib restored the activity of GSK-3β and attenuated Treg cell function. β-TrCP was involved in GSK-3β-mediated Foxp3 degradation, and mass spectrometry identified Lys³⁵⁶ as the ubiquitination site of Foxp3 by β-TrCP. These findings demonstrate the posttranslational regulation of Foxp3 expression by AREG in cancer patients through AREG/EGFR/GSK-3β signaling, which could lead to Foxp3 protein degradation in Treg cells and a potential therapeutic target for cancer treatment.

Wang C, et al. Allergy Asthma Immunol Res. 2022 Nov;14(6):604-652. https://doi.org/10.4168/aair.2022.14.6.604

Conclusion. Thymic stromal lymphopoietin (TSLP) played an important role in the pathogenesis of allergic rhinitis (AR) and can be regarded a potential therapeutic target for the management of AR. Objective. To evaluate the possible role of TSLP in the pathogenesis of AR. Patients and methods. We enrolled 16 patients of AR to investigate the expression of TSLP in nasal mucosa and evaluate the link of TSLP and interleukin-4 (IL-4). Expression of TSLP was detected by immunohistochemical analysis and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and concentrations of TSLP and IL-4 were measured by enzyme-linked immunosorbent assay (ELISA). Results. TSLP was detected in all samples and the mRNA and protein expression of TSLP is increased significantly in AR nasal mucosa compared with normal control (P<0.05). TSLP production is tightly correlated with IL-4 and severity of AR (P<0.05).

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines-with a focus on China-will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.