Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United States.
Department of Otolaryngology-Head and Neck Surgery, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, United States.
Oral Oncol. 2018 Feb;77:83-89. doi: 10.1016/j.oraloncology.2017.12.003. Epub 2017 Dec 23.
Tumor infiltrating lymphocytes (TILs) have been shown to be an important prognostic factor in patients with previously untreated head and neck cancer. After organ preservation therapy for laryngeal cancer and subsequent persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to determine if TILs have value as a prognostic biomarker in patients with surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma. Levels of TILs were quantified on tissue microarrays from 183 patients undergoing salvage total laryngectomy for persistent/recurrent laryngeal cancer after radiation or chemoradiation between 1997 and 2014. Demographic and clinical data were abstracted. Immunohistology evaluation included CD4, CD8, PDL-1, p16, CD31, Vimentin, EGFR, and p53. Elevated levels of either CD8 or CD4 positive TILs were associated with improved disease specific survival (CD8: HR 0.46, 95% CI 0.24-0.88, CD4: HR 0.43; 95% CI 0.21-0.89) and disease free survival (CD8: HR 0.53, 95% CI 0.29-0.94, CD4: HR 0.52; 95% CI 0.27-0.99). Levels of CD8 (HR 0.74; 95% CI 0.47-1.17) or CD4 (HR 0.66; 95% CI 0.40-1.08) TILs were not significantly associated with overall survival. In bivariate analysis, patients with elevated CD4 and/or CD8 TILs had significantly improved disease specific survival (HR 0.42; 95% CI 0.21-0.83) and disease free survival (HR 0.45; 95% CI 0.24-0.84) compared to patients with low levels of CD4 and CD8. PDL-1, p16, CD31, Vimentin, EGFR, and p53 were not significant prognostic factors. On multivariate analysis, elevated CD8 TILs were associated with improved disease specific survival (HR 0.35; 95% CI 0.14-0.88, p = .02) and disease free survival (HR 0.41; 95% CI 0.17-0.96, p = .04). CD8, and possibly CD4, positive TILs are associated with favorable disease free and disease specific survival for recurrent/persistent laryngeal cancer.
肿瘤浸润淋巴细胞（TILs）已被证明是未经治疗的头颈部癌症患者的一个重要预后因素。在喉癌的器官保存治疗后，随后的持续性/复发性，TILs 的预后价值尚不清楚。我们的目标是确定 TILs 是否可作为可手术挽救的持续性/复发性喉鳞状细胞癌患者的预后生物标志物。在 1997 年至 2014 年间，对 183 例接受挽救性全喉切除术的复发性/持续性喉癌患者的组织微阵列进行了 TILs 水平的定量分析。提取了人口统计学和临床数据。免疫组织学评估包括 CD4、CD8、PDL-1、p16、CD31、波形蛋白、EGFR 和 p53。CD8 或 CD4 阳性 TIL 水平升高与疾病特异性生存（CD8：HR 0.46，95%CI 0.24-0.88，CD4：HR 0.43；95%CI 0.21-0.89）和无病生存（CD8：HR 0.53，95%CI 0.29-0.94，CD4：HR 0.52；95%CI 0.27-0.99）改善相关。CD8（HR 0.74；95%CI 0.47-1.17）或 CD4（HR 0.66；95%CI 0.40-1.08）TIL 水平与总生存无显著相关性。在双变量分析中，与 CD4 和/或 CD8 TIL 水平低的患者相比，CD4 和/或 CD8 TIL 水平升高的患者疾病特异性生存（HR 0.42；95%CI 0.21-0.83）和无病生存（HR 0.45；95%CI 0.24-0.84）显著改善。PDL-1、p16、CD31、波形蛋白、EGFR 和 p53 不是显著的预后因素。多变量分析显示，CD8 TIL 升高与疾病特异性生存（HR 0.35；95%CI 0.14-0.88，p=0.02）和无病生存（HR 0.41；95%CI 0.17-0.96，p=0.04）改善相关。CD8 和可能的 CD4 阳性 TIL 与复发性/持续性喉癌的无病生存和疾病特异性生存相关。
