肿瘤突变负担、炎症基因表达谱和 PD-L1 表达对头颈部鳞状细胞癌患者对 pembrolizumab 反应的影响。

Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma.

机构信息

Department of Medical Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA

Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, USA.

出版信息

J Immunother Cancer. 2022 Feb;10(2). doi: 10.1136/jitc-2021-003026.

BACKGROUND

To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study.

METHODS

Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV, mapping >20 HPV reads) in pretreatment tumor samples (n=106).

RESULTS

TMB, clonality-weighted TMB, and TcellGEP were significantly associated with objective response (p0.0276, p0.0201, and p0.006, respectively), and a positive trend was observed between NL and PD-L1 CPS and clinical response (p0.0550 and p0.0682, respectively). No correlation was observed between TMB and TcellGEP (Spearman ρ=-0.026) or TMB and PD-L1 (Spearman ρ=0.009); a correlation was observed between TcellGEP and PD-L1 (Spearman ρ=0.511). HPV status by WES and p16 immunohistochemistry showed concordance (84% ҡ=0.573) among patients whose HPV results were available using both methods.

CONCLUSIONS

TMB and inflammatory biomarkers (TcellGEP and PD-L1) may represent distinct and complementary biomarkers predicting response to anti-programmed death 1 therapies in HNSCC; further study of these relationships in randomized clinical trials is needed.

TRIAL REGISTRATION NUMBER

NCT01848834.

背景

在 KEYNOTE-012 研究中，对复发性/转移性（R/M）头颈部鳞状细胞癌（HNSCC）患者接受派姆单抗治疗的反应的基因组决定因素进行特征分析。

方法

在 192 例 R/M HNSCC 患者中，评估了生物标志物（肿瘤突变负担（TMB）、新抗原负荷（NL）、18 基因 T 细胞炎症基因表达谱（TcellGEP）和 PD-L1 联合阳性评分（CPS））与派姆单抗临床结局之间的相关性。在预处理肿瘤样本中（n=106），还使用 p16 免疫组化和全外显子组测序（WES；HPV，映射>20 HPV 读数）评估了肿瘤人乳头瘤病毒（HPV）状态。

结果

TMB、克隆性加权 TMB 和 TcellGEP 与客观缓解显著相关（p0.0276、p0.0201 和 p0.006），NL 和 PD-L1 CPS 与临床反应之间呈正相关趋势（p0.0550 和 p0.0682）。TMB 与 TcellGEP（Spearman ρ=-0.026）或 TMB 与 PD-L1（Spearman ρ=0.009）之间无相关性；TcellGEP 与 PD-L1 之间存在相关性（Spearman ρ=0.511）。使用两种方法均可获得 HPV 结果的患者中，WES 和 p16 免疫组化的 HPV 状态具有一致性（84% κ=0.573）。