Burcher Kimberly M, Lantz Jeffrey W, Gavrila Elena, Abreu Arianne, Burcher Jack T, Faucheux Andrew T, Xie Amy, Jackson Clayton, Song Alexander H, Hughes Ryan T, Lycan Thomas, Bunch Paul M, Furdui Cristina M, Topaloglu Umit, D'Agostino Ralph B, Zhang Wei, Porosnicu Mercedes
Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.
Lewisgale Medical Center, Salem, VA 24153, USA.
Cancers (Basel). 2021 Nov 16;13(22):5733. doi: 10.3390/cancers13225733.
Failure to predict response to immunotherapy (IO) limited its benefit in the treatment of head and neck squamous cell cancer (HNSCC) to 20% of patients or less. Biomarkers including tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) were evaluated as predictors of response to IO, but the results are inconsistent and with a lack of standardization of their methods. In this retrospective study, TMB and PD-L1 were measured by commercially available methodologies and were correlated to demographics, outcome, and response to PD-1 inhibitors. No correlation was found between TMB and PD-L1 levels. High TMB was associated with smoking and laryngeal primaries. PD-L1 was significantly higher in African Americans, patients with earlier stage tumors, nonsmokers, and nonethanol drinkers. Patients with high TMB fared better in univariate and multivariate survival analysis. No correlation was found between PD-L1 expression and prognosis. There was a statistically significant association between PFS and response to IO and TMB. There was no association between response to ICI and PD-L1 in this study, possibly affected by variations in the reporting method. Further studies are needed to characterize the biomarkers for IO in HNSCC, and this study supports further research into the advancement of TMB in prospective studies.
无法预测免疫疗法（IO）的疗效限制了其在头颈部鳞状细胞癌（HNSCC）治疗中的受益患者比例至20%或更低。包括肿瘤突变负荷（TMB）和程序性死亡配体-1（PD-L1）在内的生物标志物被评估为IO疗效的预测指标，但结果不一致且其方法缺乏标准化。在这项回顾性研究中，TMB和PD-L1通过市售方法进行测量，并与人口统计学、结局以及对PD-1抑制剂的反应相关联。未发现TMB与PD-L1水平之间存在相关性。高TMB与吸烟和喉原发性肿瘤相关。非洲裔美国人、肿瘤分期较早的患者、不吸烟者和不饮酒者的PD-L1水平显著更高。在单变量和多变量生存分析中，高TMB的患者预后较好。未发现PD-L1表达与预后之间存在相关性。无进展生存期（PFS）与IO反应和TMB之间存在统计学显著关联。在本研究中，免疫检查点抑制剂（ICI）反应与PD-L1之间无关联，这可能受报告方法差异的影响。需要进一步研究以明确HNSCC中IO的生物标志物，并且本研究支持在前瞻性研究中进一步探索TMB的进展。
