Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2012;7(6):e38711. doi: 10.1371/journal.pone.0038711. Epub 2012 Jun 12.
Human papillomavirus (HPV) is a causative factor for tonsillar squamous cell carcinoma (TSCC) and patients with HPV positive (HPV(+)) TSCC have a better clinical outcome than those with HPV negative (HPV(-)) TSCC. However, since not all patients with HPV(+) TSCC respond to treatment, additional biomarkers are needed together with HPV status to better predict response to therapy and to individualize treatment. For this purpose, we examined whether the number of tumor infiltrating cytotoxic and regulatory T-cells in TSCC correlated to HPV status and to clinical outcome.
Formalin fixed paraffin embedded TSCC, previously analysed for HPV DNA, derived from 83 patients, were divided into four groups depending on the HPV status of the tumor and clinical outcome. Tumors were stained by immunohistochemistry and evaluated for the number of infiltrating cytotoxic (CD8(+)) and regulatory (Foxp3(+)) T-cells.
A high CD8(+) T-cell infiltration was significantly positively correlated to a good clinical outcome in both patients with HPV(+) and HPV(-) TSCC patients. Similarly, a high CD8(+)/Foxp3(+) TIL ratio was correlated to a 3-year disease free survival. Furthermore, HPV(+) TSCC had in comparison to HPV(-) TSCC, higher numbers of infiltrating CD8(+) and Foxp3(+) T-cells.
In conclusion, a positive correlation between a high number of infiltrating CD8(+) cells and clinical outcome indicates that CD8(+) cells may contribute to a beneficial clinical outcome in TSCC patients, and may potentially serve as a biomarker. Likewise, the CD8(+)/Foxp3(+)cell ratio can potentially be used for the same purpose.
人乳头瘤病毒（HPV）是扁桃体鳞状细胞癌（TSCC）的致病因素，HPV 阳性（HPV(+））的 TSCC 患者比 HPV 阴性（HPV(-））的 TSCC 患者有更好的临床结局。然而，由于并非所有 HPV(+)TSCC 患者对治疗有反应，因此需要额外的生物标志物与 HPV 状态一起使用，以更好地预测对治疗的反应并实现个体化治疗。为此，我们研究了 TSCC 中浸润性细胞毒性和调节性 T 细胞的数量是否与 HPV 状态和临床结局相关。
从 83 名患者中提取了先前分析 HPV DNA 的福尔马林固定石蜡包埋的 TSCC，根据肿瘤的 HPV 状态和临床结局将其分为四组。通过免疫组织化学染色评估浸润性细胞毒性（CD8(+））和调节性（Foxp3(+））T 细胞的数量。
高 CD8(+)T 细胞浸润与 HPV(+)和 HPV(-)TSCC 患者的良好临床结局显著正相关。同样，高 CD8(+)/Foxp3(+)TIL 比值与 3 年无病生存率相关。此外，与 HPV(-)TSCC 相比，HPV(+)TSCC 浸润的 CD8(+)和 Foxp3(+)T 细胞数量更高。
总之，大量浸润的 CD8(+)细胞与临床结局之间的正相关表明 CD8(+)细胞可能有助于 TSCC 患者获得有益的临床结局，并可能作为生物标志物。同样，CD8(+)/Foxp3(+)细胞比值也可用于相同目的。
