Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial.

BACKGROUND: Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC. MATERIALS AND METHODS: A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate. RESULTS: The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR. CONCLUSION: Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570.

Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis.

Introduction: Previous studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear. Methods: We collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC. Results: Patients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04-12.77, p = 0.004). Conclusions: The present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.

Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4.

Bladder cancer (BLCA) is a common genitourinary cancer in patients, and tumour angiogenesis is indispensable for its occurrence and development. However, the indepth mechanism of tumour angiogenesis in BLCA remains elusive. According to recent studies, the tight junction protein family member occludin (OCLN) is expressed at high levels in BLCA tissues and correlates with a poor prognosis. Downregulation of OCLN inhibits tumour angiogenesis in BLCA cells and murine xenografts, whereas OCLN overexpression exerts the opposite effect. Mechanistically, the RT-qPCR analysis and Western blotting results showed that OCLN increased interleukin-8 (IL8) and p-signal transducer and activator of transcription 3 (STAT3) levels to promote BLCA angiogenesis. RNA sequencing analysis and dual-luciferase reporter assays indicated that OCLN regulated IL8 transcriptional activity via the transcription factor STAT4. In summary, our results provide new perspectives on OCLN, as this protein participates in the development of BLCA angiogenesis by activating the IL8/STAT3 pathway via STAT4 and may serve as a novel and unique therapeutic target.