Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto; University of Toronto, Toronto, Canada.
Medical Oncology Department, Catalan Institute of Oncology (ICO), ONCOBELL-IDIBELL, L'Hospitalet de Llobregat, Barcelona; Barcelona University, Barcelona.
Ann Oncol. 2019 Jan 1;30(1):57-67. doi: 10.1093/annonc/mdy507.
Anti-programmed cell death protein 1 (PD-1) agents have become the standard of care for platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and are currently being evaluated in various disease settings. However, despite the gain in overall survival seen in some of the clinical trials, the majority of patients display primary resistance and do not benefit from these agents. Taking into consideration the potentially severe immune-related toxicities and their high cost, the search for predictive biomarkers of response is crucial. Besides Programmed death ligand-1 (PD-L1) expression, other biomarkers such as immune infiltration, tumor mutational burden or immune-gene expression profiling have been explored, but none of them has been validated in this disease. Among these, the microbiota has recently garnered tremendous interest since it has proven to influence the efficacy of PD-1 blockade in some tumor types. With the accumulating evidence on the effect of the microbiota in HNSCC tumorigenesis and progression, the study of its potential role as a predictive immune biomarker is warranted. This review examines the available evidence on emerging immune predictive biomarkers of response to anti-PD-1/PD-L1 therapy in HNSCC, introducing the microbiota and its potential use as a predictive immune biomarker in this disease.
抗程序性细胞死亡蛋白 1（PD-1）药物已成为铂类难治性复发性/转移性头颈部鳞状细胞癌（HNSCC）的标准治疗方法，目前正在各种疾病环境中进行评估。然而，尽管一些临床试验中观察到总生存期的提高，但大多数患者表现出原发性耐药，并且不能从这些药物中获益。考虑到潜在的严重免疫相关毒性及其高昂的成本，寻找预测反应的生物标志物至关重要。除程序性死亡配体-1（PD-L1）表达外，还探索了其他生物标志物，如免疫浸润、肿瘤突变负担或免疫基因表达谱，但在这种疾病中没有一种得到验证。在这些标志物中，微生物组最近引起了极大的兴趣，因为它已被证明可以影响某些肿瘤类型中 PD-1 阻断的疗效。随着越来越多的证据表明微生物组在 HNSCC 肿瘤发生和进展中的作用，研究其作为预测免疫生物标志物的潜在作用是有必要的。这篇综述探讨了在 HNSCC 中，抗 PD-1/PD-L1 治疗反应的新兴免疫预测生物标志物的现有证据，介绍了微生物组及其在该疾病中作为预测免疫生物标志物的潜在用途。
