IL-12Rβ2 阳性肿瘤浸润淋巴细胞比例高提示喉癌预后良好。
A high ratio of IL-12Rβ2-positive tumor-infiltrating lymphocytes indicates favorable prognosis in laryngeal cancer.
机构信息
Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230061, China; Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing, China.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Oral Oncol. 2017 Nov;74:148-156. doi: 10.1016/j.oraloncology.2017.10.006. Epub 2017 Oct 16.
BACKGROUND
The purpose of this study was to elucidate IL-12Rβ2's roles as a tumor-associated immunological molecule, delineate the complex roles of IL-12Rβ2 tumor-infiltrating lymphocytes (TILs) and tumor cell IL-12Rβ2 expression in the tumor microenvironment, and determine the correlation of IL-12Rβ2 TILs and tumor cell IL-12Rβ2 expression with clinical prognosis.
METHODS
We assessed mRNA and protein levels in matched laryngeal cancer tissues (LTs) and adjacent normal mucous membrane tissues (ANMMTs) from 3 laryngeal cancer (LC) patients and ratios of IL-12Rβ2 TILs in matched LTs and ANMMTs from 61 LC patients. We used the Kaplan-Meier log-rank test and Cox regression hazard ratios to analyze survival.
RESULTS
Comparative proteomic and transcriptomic assays revealed that matched LTs and ANMMTs from the 3 patients had significantly different IL-12Rβ2 and IFN-γ expression; the ratio of IL-12Rβ2 TILs decreased with lower degrees of tumor differentiation. Among all 61 LC patients, the IL-12Rβ2 TIL ratio in ANMMTs (38.5% ± 22.8%) was significantly higher than that in LTs (29.7% ± 19%; p<.001). Kaplan-Meier analysis revealed that patients with an IL-12Rβ2 TIL ratio ≥35% had significantly better survival than those with an IL-12Rβ2 TIL ratio <35% (log rank p=0.041). Multivariable analysis showed a significant association between a high IL-12Rβ2 TIL ratio and overall survival (hazard ratio, 0.14; 95% confidence interval, 0.03-0.77).
CONCLUSION
Tumor cell differentiation is associated with TILs' expression of IL-12Rβ2, and an IL-12Rβ2 TIL ratio ≥35%) indicates favorable prognosis in LC.
背景
本研究旨在阐明白细胞介素-12 受体β2（IL-12Rβ2）作为肿瘤相关免疫分子的作用，阐明肿瘤微环境中 IL-12Rβ2 肿瘤浸润淋巴细胞（TIL）和肿瘤细胞 IL-12Rβ2 表达的复杂作用，并确定 IL-12Rβ2 TILs 与肿瘤细胞 IL-12Rβ2 表达与临床预后的相关性。
方法
我们评估了 3 例喉癌（LC）患者的配对喉癌组织（LTs）和相邻正常黏膜组织（ANMMTs）的 mRNA 和蛋白水平，以及 61 例 LC 患者的配对 LTs 和 ANMMTs 中 IL-12Rβ2 TIL 的比例。我们使用 Kaplan-Meier 对数秩检验和 Cox 回归风险比分析生存情况。
结果
比较蛋白质组学和转录组学检测结果显示，3 例患者的配对 LTs 和 ANMMTs 的 IL-12Rβ2 和 IFN-γ表达有显著差异；IL-12Rβ2 TIL 的比例随着肿瘤分化程度的降低而降低。在所有 61 例 LC 患者中，ANMMTs 中的 IL-12Rβ2 TIL 比例（38.5%±22.8%）明显高于 LTs（29.7%±19%；p<.001）。Kaplan-Meier 分析显示，IL-12Rβ2 TIL 比例≥35%的患者的生存情况明显优于 IL-12Rβ2 TIL 比例<35%的患者（对数秩检验 p=0.041）。多变量分析显示，高 IL-12Rβ2 TIL 比例与总生存时间之间存在显著相关性（风险比，0.14；95%置信区间，0.03-0.77）。
结论
肿瘤细胞分化与 TILs 表达的 IL-12Rβ2 有关，IL-12Rβ2 TIL 比例≥35%提示 LC 预后良好。
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