Zhujiang Dai

Crohn’s disease is a highly heterogeneous autoimmune disease with a unique inflammatory phenotype of T cells at the lesion site. We aim to further explore the diagnosis of Crohn’s disease and drug prediction of T cell marker gene expression. We obtained single-cell expression profile data from 22 CDs or normal samples and performed cell annotation and cellular communication analysis. Through the intersection of T cell marker genes, differential genes, and WGCNA results, we identified T cell-specific key genes and their immune landscapes and potential pathogenesis, and validated them across multiple datasets and patient tissue samples. We also explored the differentiation characteristics of genes by pseudo-temporal analysis and assessed their diagnostic performance and drug sensitivity by molecular docking. Finally, we extended this study to the prognosis of IBD-associated colon cancer. TNF-centered 5-gene diagnostic model not only has excellent diagnostic efficacy, but is also closely associated with KRAS, P53, and IL6/JAK/STAT3 pathways and physiological processes, such as EMT, coagulation, and apoptosis. In addition, this diagnostic model may have potential synergistic immunotherapeutic effects, with positive correlations with immune checkpoints such as CTLA4, CD86, PDCD1LG2, and CD40. Molecular docking demonstrated that BIRC3 and ANXA1 have strong binding properties to Azathioprine and Glucoocorticoid. Furthermore, the 5-gene model may suggest antagonism to IFX and prognosis for colon cancer associated with inflammatory bowel disease. Single-cell sequencing targeting T cell-related features in patients with Crohn’s disease may aid in new diagnostic decisions, as well as the initial exploration of high-potential therapies.

In recent years, cancer immunotherapy has become a breakthrough method to solve solid tumors. It uses immune checkpoint inhibitors to interfere with tumor immune escape to coordinate anti-tumor therapy. However, immunotherapy has an individualized response rate. Moreover, immune-related adverse events and drug resistance are still urgent issues that need to be resolved, which may be attributed to the immune imbalance caused by immune checkpoint inhibitors. Microbiome research has fully revealed the metabolic-immune interaction relationship between the microbiome and the host. Surprisingly, sequencing technology further proved that intestinal microbiota could effectively intervene in tumor immunotherapy and reduce the incidence of adverse events. Therefore, cancer immunotherapy under the intervention of intestinal microbiota has innovatively broadened the anti-tumor landscape and is expected to become an active strategy to enhance individualized responses.