Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Int J Cancer. 2012 Jul 15;131(2):E74-85. doi: 10.1002/ijc.26497. Epub 2011 Nov 19.
Squamous cell carcinomas of the head and neck (HNSCC), in particular those of the oropharynx, can be caused by human papilloma virus Type 16 (HPV16). Whereas these HPV-induced oropharyngeal carcinomas may express the HPV16 E6 and E7 oncoproteins and are associated with better survival, the nonvirally induced HNSCC are associated with overexpression of p53. In this study we assessed the presence of systemic and local T cells reactive against these oncoproteins in HNSCC. An exploratory study on the presence, type and function of HPV16- and/or p53-specific T cells in the blood, tumor and/or metastatic lymph node as measured by several immune assays was performed in an unselected group of 50 patients with HNSCC. Tumor tissue was tested for HPV DNA and the overexpression of p53 protein. Almost all HPV16+ tumors were located in the oropharynx. Circulating HPV16- and p53-specific T cells were found in 17/47 and 7/45 tested patients. T cells were isolated from tumor cultures and/or lymph nodes of 20 patients. HPV16-specific T cells were detected in six of eight HPV+ tumors, but in none of the 12 HPV-tumors. Tumor-infiltrating p53-specific T cells were not detected. In depth analysis of the HPV16-specific T-cell response revealed that this response comprised a broad repertoire of CD4+ T-helper Type 1 and 2 cells, CD4+ regulatory T cells and CD8+ T cells reactive to HPV16. The local presence of HPV16-specific T-cell immunity in HPV16-induced HNSCC implicates a role in the antitumor response and support the development of immunotherapy for HNSCC.
头颈部鳞状细胞癌（HNSCC），特别是口咽癌，可由人乳头瘤病毒 16 型（HPV16）引起。虽然这些 HPV 诱导的口咽癌可能表达 HPV16 的 E6 和 E7 癌蛋白，与更好的生存相关，但非病毒诱导的 HNSCC 与 p53 的过度表达相关。在这项研究中，我们评估了 HNSCC 中针对这些癌蛋白的全身性和局部 T 细胞的存在情况。通过几种免疫检测方法，在 50 例未选择的 HNSCC 患者中进行了一项关于 HPV16 和/或 p53 特异性 T 细胞在血液、肿瘤和/或转移性淋巴结中的存在、类型和功能的探索性研究。对肿瘤组织进行 HPV DNA 检测和 p53 蛋白过表达检测。几乎所有 HPV16+肿瘤均位于口咽部。在 47 例接受检测的患者中有 17 例和在 45 例接受检测的患者中有 7 例循环中存在 HPV16 和 p53 特异性 T 细胞。从 20 例患者的肿瘤培养物和/或淋巴结中分离出 T 细胞。在 8 例 HPV+肿瘤中有 6 例检测到 HPV16 特异性 T 细胞，但在 12 例 HPV-肿瘤中均未检测到。未检测到肿瘤浸润性 p53 特异性 T 细胞。对 HPV16 特异性 T 细胞反应的深入分析表明，该反应包含广泛的 CD4+ T 辅助 1 型和 2 型细胞、CD4+调节性 T 细胞和 CD8+ T 细胞对 HPV16 的反应。HPV16 诱导的 HNSCC 中 HPV16 特异性 T 细胞免疫的局部存在提示其在抗肿瘤反应中起作用，并支持为 HNSCC 开发免疫疗法。
