Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Laryngoscope. 2012 Jan;122(1):121-7. doi: 10.1002/lary.22133.
OBJECTIVES/HYPOTHESIS: Human papillomavirus-16 (HPV-16)-associated carcinoma of the oropharynx has a favorable prognosis. Such patients have elevated CD8+ T-lymphocyte levels that correlate with response to chemotherapy and survival. Tumor-infiltrating lymphocyte (TIL) subpopulations were assessed in pretreatment biopsies from a prospective patient cohort to determine if TIL subsets differed by HPV status, clinical factors, or patient outcome or correlated with peripheral blood T-cell levels.
Retrospective immunological correlative study of patients entered in a prospective Phase 2 clinical trial.
Measured were CD8, CD4, CD68, and Treg (FoxP3) lymphocytes by immunohistochemistry in a tissue microarray created from patients (n=46) with advanced oropharyngeal cancer. Correlations with peripheral blood levels, HPV status, expression of epidermal growth factor receptor (EGFR), clinical tumor, and patient characteristics and outcome were determined. Median follow-up was 6.6 years.
HPV-16-positive patients had improved survival (P=.016). Degree of T-cell infiltration did not differ by HPV status but was significantly related to disease-specific survival (DSS) and overall survival (OS). Even after adjusting for HPV status, we found that CD8, FoxP3, and total T cells were significantly associated with DSS (P=.0236, P=.0040, and P=.0197, respectively) and OS (P=.0137, P=.0158, and P=.0115, respectively). Less T-cell infiltration (P=.0130) and CD4 cells in particular (P=.0792) were associated with higher EGFR expression.
Improved outcomes are associated with increased TILs independent of HPV status and suggest the local immune response may be more related to factors such as tumor size, EGFR expression, or performance status than HPV status. Further study of larger numbers of patients and infiltrates combined with functional analysis of individual subsets may be necessary to detect significant differences in local immunity in HPV-16-related cancers.
目的/假说：人乳头瘤病毒 16 型（HPV-16）相关口咽癌预后良好。此类患者 CD8+T 淋巴细胞水平升高，与化疗反应和生存相关。本研究通过评估预处理活检中的肿瘤浸润淋巴细胞（TIL）亚群，以确定 TIL 亚群是否因 HPV 状态、临床因素或患者结局而不同，或与外周血 T 细胞水平相关。
对前瞻性 2 期临床试验入组的患者进行回顾性免疫相关性研究。
通过免疫组织化学方法在晚期口咽癌患者的组织微阵列中测量 CD8、CD4、CD68 和 Treg（FoxP3）淋巴细胞。分析与外周血水平、HPV 状态、表皮生长因子受体（EGFR）表达、临床肿瘤及患者特征和结局的相关性。中位随访时间为 6.6 年。
HPV-16 阳性患者的生存改善（P=.016）。T 细胞浸润程度与 HPV 状态无关，但与疾病特异性生存（DSS）和总生存（OS）显著相关。即使调整 HPV 状态后，我们发现 CD8、FoxP3 和总 T 细胞与 DSS（P=.0236、P=.0040 和 P=.0197）和 OS（P=.0137、P=.0158 和 P=.0115）显著相关。T 细胞浸润减少（P=.0130），特别是 CD4 细胞（P=.0792）与 EGFR 表达升高相关。
与 HPV 状态无关，改善结局与 TIL 增加相关，提示局部免疫反应可能与肿瘤大小、EGFR 表达或一般状态等因素相关，而与 HPV 状态关系不大。需要对更多患者和浸润物进行更大规模的研究，并对个体亚群的功能进行分析，以检测 HPV-16 相关癌症中局部免疫的差异。
