Relationship between Tumor Mutational Burden, PD-L1, Patient Characteristics, and Response to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma.
Relationship between Tumor Mutational Burden, PD-L1, Patient Characteristics, and Response to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma.
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DOI：
10.3390/cancers13225733
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发表时间：
2021-11-16
期刊：
影响因子：
5.2
通讯作者：
Porosnicu M
中科院分区：
文献类型：
--
作者：
Burcher KM;Lantz JW;Gavrila E;Abreu A;Burcher JT;Faucheux AT;Xie A;Jackson C;Song AH;Hughes RT;Lycan T Jr;Bunch PM;Furdui CM;Topaloglu U;D'Agostino RB Jr;Zhang W;Porosnicu M
免疫疗法促使头颈鳞状细胞癌（HNSCC）的管理发生了巨大变化，但是受益于治疗的患者百分比限制为20％或更少。精确肿瘤学在HNSCC中的应用引入了生物标志物出现的潜力，这些可能预测可能对免疫疗法的反应，并有助于选择可能受益于免疫检查点抑制剂治疗的患者。在这项回顾性研究中，对HNSCC肿瘤的肿瘤突变负担和编程死亡配体1测量的结果独立评估了与人口统计学，危险因素，疾病特征，生存和对ICI的反应的关联。预计这项研究的结果将有助于为创建一个框架奠定基础，其中PD-L1和TMB与其他变量共存，以在个体级别预测对ICI的反应。
未能预测对免疫疗法（IO）的反应将其在治疗头颈鳞状细胞癌（HNSCC）治疗中的好处限制为患者的20％或更少。评估了包括肿瘤突变负担（TMB）和程序性死亡配体1（PD-L1）在内的生物标志物作为对IO反应的预测指标，但结果不一致，并且缺乏其方法的标准化。在这项回顾性研究中，TMB和PD-L1通过市售方法测量，并与人口统计学，结果和对PD-1抑制剂的反应相关。在TMB和PD-L1水平之间未发现相关性。高TMB与吸烟和喉的初选有关。非洲裔美国人，较早阶段肿瘤，非吸烟者和非乙醇饮用者的患者的PD-L1明显更高。 TMB高的患者在单变量和多元生存分析方面表现更好。 PD-L1表达和预后之间没有发现相关性。 PFS与IO和TMB的响应之间存在统计学意义的关联。在这项研究中，对ICI和PD-L1的反应之间没有关联，可能会受到报告方法的变化的影响。需要进一步的研究来表征HNSCC中IO的生物标志物，这项研究支持对前瞻性研究中TMB进步的进一步研究。
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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影响因子：
10.1
作者：
Johnson DB;Frampton GM;Rioth MJ;Yusko E;Xu Y;Guo X;Ennis RC;Fabrizio D;Chalmers ZR;Greenbowe J;Ali SM;Balasubramanian S;Sun JX;He Y;Frederick DT;Puzanov I;Balko JM;Cates JM;Ross JS;Sanders C;Robins H;Shyr Y;Miller VA;Stephens PJ;Sullivan RJ;Sosman JA;Lovly CM
通讯作者：
Lovly CM
DOI：
10.1016/j.ijom.2017.09.006
发表时间：
2018-05-01
影响因子：
2.4
作者：
Hanna, G. J.;Woo, S. -B.;Loral, J. H.
通讯作者：
Loral, J. H.
影响因子：
8.4
作者：
Eder, T.;Hess, A. K.;Tinhofer, I
通讯作者：
Tinhofer, I
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D
DOI：
10.1056/nejmoa1801946
发表时间：
2018-05-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hellmann MD;Ciuleanu TE;Pluzanski A;Lee JS;Otterson GA;Audigier-Valette C;Minenza E;Linardou H;Burgers S;Salman P;Borghaei H;Ramalingam SS;Brahmer J;Reck M;O'Byrne KJ;Geese WJ;Green G;Chang H;Szustakowski J;Bhagavatheeswaran P;Healey D;Fu Y;Nathan F;Paz-Ares L
通讯作者：
Paz-Ares L