Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia.
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Cancer Immunol Res. 2018 Mar;6(3):295-304. doi: 10.1158/2326-6066.CIR-17-0299. Epub 2018 Jan 29.
Human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV OPSCC) represents a distinct subgroup of head and neck cancers associated with clinical outcomes that are not accurately categorized by existing tumor-node-metastasis-based staging methods. Given the significant impact of immune parameters, such as tumor-infiltrating lymphocytes (TIL) in many cancers, we sought to determine if immunophenotyping tumors can improve categorization of HPV OPSCCs for prognostic purposes. In a cohort of 190 patients with HPV OPSCC, we quantified and determined the localization of CD8 TILs, as well as PD-L1-expressing tumor cells (TC) and immune cells (IC). The prognostic significance of these parameters on overall survival (OS) was evaluated, and their contribution to existing prognostic models was determined. High CD8 TIL abundance (≥30% on stromal or intratumoral ICs) was seen in 61.3% patients and was associated with improved OS [HR, 0.4; 95% confidence interval (CI), 0.2-0.9; = 0.017]. Although the expression of PD-L1 on TC was not prognostic, high expression of PD-L1 on ≥5% of intratumoral ICs was found in 38.5% patients and was significantly associated with improved OS (HR, 0.37; 95% CI, 0.15-0.93; = 0. 023). Both high intratumoral IC PD-L1 expression and abundant CD8 TILs in HPV OPSCCs identify subgroups of patients with excellent outcomes and provide additional prognostic information beyond existing staging systems. .
人乳头瘤病毒阳性口咽鳞状细胞癌(HPV OPSCC)代表了一组与临床结果相关的头颈部癌症,这些结果不能通过现有的基于肿瘤-淋巴结-转移的分期方法准确分类。鉴于免疫参数(如肿瘤浸润淋巴细胞[TIL])在许多癌症中的重要影响,我们试图确定免疫表型肿瘤是否可以改善 HPV OPSCC 的分类,以达到预后目的。在 190 例 HPV OPSCC 患者的队列中,我们定量并确定了 CD8 TIL、PD-L1 表达的肿瘤细胞(TC)和免疫细胞(IC)的定位。评估了这些参数对总生存(OS)的预后意义,并确定了它们对现有预后模型的贡献。在 61.3%的患者中观察到高 CD8 TIL 丰度(间质或肿瘤内 IC 上≥30%),并与 OS 改善相关[HR,0.4;95%置信区间(CI),0.2-0.9;P = 0.017]。尽管 TC 上 PD-L1 的表达与预后无关,但在 38.5%的患者中发现肿瘤内 IC 上≥5%的 PD-L1 表达与 OS 改善显著相关(HR,0.37;95%CI,0.15-0.93;P = 0.023)。HPV OPSCC 中高肿瘤内 IC PD-L1 表达和丰富的 CD8 TIL 可识别具有良好结局的患者亚组,并提供了超出现有分期系统的额外预后信息。