Institute of Pathology, Charité Hospital, Berlin, Germany.
Institute of Pathology, University Hospital Dresden, Dresden, Germany.
Cancer Immunol Immunother. 2019 Sep;68(9):1443-1454. doi: 10.1007/s00262-019-02378-w. Epub 2019 Aug 23.
Immunotherapy is effective in head and neck squamous cell carcinoma (HNSCC), but only a minority of patients responds to immune checkpoint blockade (ICB). To contribute to a better understanding of the underlying immune biology, we combined histomorphological evaluation and molecular analysis of the HNSCC immune microenvironment in the TCGA cohort. Analyzing digital HE-stained slides, a method for classification of tumor infiltrating lymphocytes (TILs) in the intra-epithelial compartment (ieTILs, present vs. absent) and the stromal compartment (strTILs, high vs. low) was established. We also analyzed the abundance of eight immune cell populations (estimated from RNAseq data) and PD-L1 mRNA expression. Status of ieTILs and status of strTILs were concordant for 61%, but discordant for 39% of tumors. In univariate survival analysis, ieTILs were a positive prognostic marker for DFS in the study cohort (HR = 0.66, p = 0.015) and in the HPV- subcohort (HR = 0.68, p = 0.04), but not in the HPV + subcohort. T cells were a positive prognostic marker for DFS in the study cohort (HR = 0.80, p = 0.03) and in the HPV + subcohort (HR = 0.20, p = 0.001), but not in the HPV- subcohort. In univariate survival analysis, PD-L1 mRNA expression was neither associated with DFS nor with OS. However, in bivariate and multivariate analyses including both PD-L1 mRNA levels and T cells, PD-L1 was a negative prognostic marker of DFS and OS, while T cells remained a positive prognostic marker. In conclusion, ieTILs and strTILs were non-redundant biomarkers in HNSCC and should be evaluated separately. The identified prognostic markers should be evaluated for predictivity in ICB-treated patients.
免疫疗法在头颈部鳞状细胞癌（HNSCC）中有效，但只有少数患者对免疫检查点阻断（ICB）有反应。为了更好地了解潜在的免疫生物学，我们结合了 TCGA 队列中 HNSCC 免疫微环境的组织形态学评估和分子分析。分析数字 HE 染色幻灯片，建立了一种用于上皮内肿瘤浸润淋巴细胞（TILs）分类的方法（即 ieTILs，存在与不存在）和基质 TILs（strTILs，高与低）。我们还分析了八种免疫细胞群体的丰度（根据 RNAseq 数据估计）和 PD-L1 mRNA 表达。ieTILs 状态和 strTILs 状态在 61%的肿瘤中一致，但在 39%的肿瘤中不一致。在单因素生存分析中，ieTILs 是研究队列（HR=0.66，p=0.015）和 HPV-亚组（HR=0.68，p=0.04）DFS 的阳性预后标志物，但在 HPV+亚组中则不是。T 细胞是研究队列（HR=0.80，p=0.03）和 HPV+亚组（HR=0.20，p=0.001）DFS 的阳性预后标志物，但在 HPV-亚组中则不是。在单因素生存分析中，PD-L1 mRNA 表达与 DFS 或 OS 均无关。然而，在包括 PD-L1 mRNA 水平和 T 细胞的双因素和多因素分析中，PD-L1 是 DFS 和 OS 的阴性预后标志物，而 T 细胞仍然是阳性预后标志物。总之，ieTILs 和 strTILs 是非冗余的 HNSCC 生物标志物，应单独评估。所确定的预后标志物应在接受 ICB 治疗的患者中进行预测性评估。
