

Functional experiments revealed that TDO2 + myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4 + T cells into Tregs and caused CD8 + T cell dysfunction. These TDO2 + myofibroblasts were located distally from tumor nests, and both CD4 + and CD8 + T cells were enriched around them.

Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). We found that tumor-infiltrating CD4 + and CD8 + T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples.

Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy.
