The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20–30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+B cells, antigen-presenting CD74+dendritic and B cells, and PD-L1+and PD-L2+myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance ofAllobaculum,Blautia,Faecalibacterium,Dorea,orRoseburiawas associated with response to the therapy. However, an increase inEnterococcuswas attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC.
美国正面临一场由高风险型人乳头瘤病毒（HPV）引发的流行病，该病毒是导致头颈部鳞状细胞癌（HNSCC）发生的主要原因。针对程序性死亡受体1（PD-1）或其配体PD-L1的免疫检查点抑制剂在HNSCC患者中疗效有限，仅观察到20%-30%的治疗应答率。因此，识别与PD-1阻断治疗反应相关的生物标志物对于改善患者预后及开发新型疗法具有重要意义。研究发现，治疗应答与活化CD27+T细胞、活化CD79a+B细胞、抗原呈递CD74+树突状细胞及B细胞，以及PD-L1+和PD-L2+髓源性抑制细胞（MDSCs）的频率增加相关。在携带舌肿瘤并接受抗PD-1治疗的小鼠中，口腔微生物群组成存在显著差异：Allobaculum、Blautia、Faecalibacterium、Dorea和Roseburia菌属丰度的升高与治疗应答相关，而Enterococcus菌属的增加则与携带舌肿瘤的无应答小鼠相关。我们的研究结果表明，随着小鼠舌肿瘤的发展及抗PD-1治疗的进行，其免疫表型、蛋白表达及细菌丰度均发生特异性改变。这些发现可能具有临床意义，特定细菌种类与免疫表型或可作为HNSCC治疗反应的生物标志物。
肿瘤(癌症)患者之家