Relationship between Tumor Mutational Burden, PD-L1, Patient Characteristics, and Response to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma

被引:24
作者
Burcher, Kimberly M. [1 ]
Lantz, Jeffrey W. [1 ]
Gavrila, Elena [1 ]
Abreu, Arianne [2 ]
Burcher, Jack T. [3 ]
Faucheux, Andrew T. [1 ]
Xie, Amy [1 ]
Jackson, Clayton [1 ]
Song, Alexander H. [1 ]
Hughes, Ryan T. [1 ]
Lycan, Thomas, Jr. [1 ]
Bunch, Paul M. [1 ]
Furdui, Cristina M. [1 ]
Topaloglu, Umit [1 ]
D'Agostino, Ralph T. B., Jr. [1 ]
Zhang, Wei [1 ]
Porosnicu, Mercedes [1 ]
机构
[1] Wake Forest Baptist Med Ctr, Winston Salem, NC 27157 USA
[2] Lewisgale Med Ctr, Salem, VA 24153 USA
[3] Lake Erie Coll Med, Bradenton, FL 34211 USA
关键词
HNSCC; TMB; immunotherapy; immune checkpoint inhibitors; PD-L1; METASTATIC HEAD; OPEN-LABEL; EXPRESSION; RECURRENT; CANCER; PEMBROLIZUMAB; IMMUNOTHERAPY; MULTICENTER; PLATINUM; BLOCKADE;
D O I
10.3390/cancers13225733
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Immunotherapy has prompted a dramatic change in the management of head and neck squamous cell carcinoma (HNSCC), but the percentage of patients benefiting from treatment is limited to 20% or less. The application of precision oncology to HNSCC introduces the potential for the emergence of biomarkers that may predict a response to immunotherapy and assist with the selection of patients that may benefit from treatment with an immune checkpoint inhibitors. In this retrospective study, the results of tumor mutational burden and programmed death ligand-1 measurements from HNSCC tumors were evaluated independently for their associations with demographics, risk factors, disease characteristics, survival, and response to ICI. Results of this study are expected to assist in laying the groundwork for creating a framework in which PD-L1 and TMB coexist with other variables to predict response to ICI on an individual level. 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.
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页数:19
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