Chinese scholars have made new progress in the immune regulation of oral mucosa

Fig.
1 Schematic diagram of TDO2+ myofibroblasts mediating CD4+/CD8⁺ T cell immunosuppression and promoting the malignant transformation of oral mucosa

Fig.
2 Mechanism of action of Pik3ip1 in regulating T cell metabolic homeostasis in regulating the progression of autoimmune diseases

With the support of the National Natural Science Foundation of China (grant numbers: 81972532, 81991500, 82101017), the team of Professor Wang Zhi of the Affiliated Stomatological Hospital of Sun Yat-sen University revealed the immune evasion characteristics of the malignant process of oral mucosa, and clarified the new mechanism
of negative immune regulation of autoimmune diseases.
The relevant research results are "TDO2+ myofibroblast-mediated immunosuppression in malignant transformation of squamous cell carcinoma (TDO2⁺ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma", published online as a cover article in the Journal of Clinical Investigation.
Links to papers: "Regulation of autoimmune disease progression by Pik3ip1 through metabolic reprogramming in T cells and therapeutic implications", published online in Science Advances (Science Advances), paper link: http://doi.
org/10.
1126/sciadv.
abo4250
.

Current immunotherapy has a low response rate in oral mucosal malignancy and many autoimmune diseases, suggesting the presence of unknown key cells and molecules
in the disease process.
The research team and the team of Professor Bai Fan of the Center for Biomedical Frontier Innovation (BIOPIC) of Peking University found that the subset of TDO2⁺ myofibroblasts can construct "traps" at the periphery of the cancer nest, and induce T cell immunosuppression through the TDO2-AhR signaling axis, promoting tumor immune escape (Figure 1).

In addition, Professor Wang's team further confirmed that the novel negative immune regulator Pik3ip1 helps maintain T cell metabolic homeostasis and regulates the progression of autoimmune diseases through the Pik3ip1/Hif1α/glycolytic axis (Figure 2).

This study proposes a new mechanism for immune evasion in the process of oral mucosal malignancy and negative immune regulation of autoimmune diseases, and also provides new targets and ideas
for blocking the process of oral mucosal malignancy in the early stage, improving the effectiveness of immunotherapy for oral cancer and precancerous lesions and autoimmune diseases.