Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

Recurrence and cancerization of ameloblastoma: multivariate analysis of 87 recurrent craniofacial ameloblastoma to assess risk factors associated with early recurrence and secondary ameloblastic carcinoma

Objective: The recurrence and progression of ameloblastoma are unpredictable. Therefore, we examined the influence of clinical factors on recurrence time and analyzed the clinical factors associated with early recurrence and cancerization. We then developed a staging system to predict early recurrence and cancerization. Methods: All of the primary craniofacial ameloblastoma patients treated in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were recorded. There were 87 recurrent cases used to create a staging system and tested in a Cox regression analysis for risk factors associated with early recurrence or cancerization following surgery. Results: There were 890 craniofacial ameloblastoma patients, and 72 cases had recurrence. There were also 15 cases with cancerous recurrence. The overall recurrence rate was 9.78%, and the cancer rate was 1.69%. The primary cases were classified into the following 3 stages based on clinicopathological features: stage I, the maximum tumor diameter <= 6 cm; stage II, the maximum diameter of tumor >6 cm or tumor invasion to the maxilla sinus/orbital floor/soft tissue; and stage III, tumor invasion of the skull base or metastasis into regional lymph nodes. When the method of surgery was controlled by partial correlation, the staging had significance with recurrence time (P=0.004). The Cox analysis showed the tumor stage was correlated with recurrence time (P=0.027) and cancerization time (P=0.002). However, the surgical method did not influence the recurrence time when adjusted for cofounding variables. Conclusions: Tumor larger than 6 cm and invasion to soft tissues or adjacent anatomical structures are associated with early recurrence. This staging system can be used to predict the risk factors of early recurrence and cancerization in ameloblastoma patients.