Tao Ye, Tao Tianchang, Gross Neil, Peng Xuyun, Li Ying, Huang Zhigang, Liu Limei, Li Guojun, Chen Xiaohong, Yang Jianming
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Beijing Tongren Eye Center, Beijing Tongren hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
Cell Physiol Biochem. 2018;50(3):1041-1054. doi: 10.1159/000494515. Epub 2018 Oct 24.
BACKGROUND/AIMS: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC).
The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival.
LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4).
IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.
背景/目的:本研究旨在从病理学角度阐明白细胞介素-12受体(IL-12R)β2和白细胞介素-23受体(IL-23R)在肿瘤微环境中的肿瘤细胞和肿瘤浸润淋巴细胞(TIL)中的表达作用,并确定它们对喉癌(LC)预后的联合影响。
通过免疫组织化学(IHC)检测61例LC患者匹配的LC组织和正常喉组织样本中IL-12Rβ2和IL-23R的肿瘤细胞表达评分和TIL阳性率。我们采用线性回归模型分析肿瘤细胞中IL-12Rβ2和IL-23R表达与TIL比率之间的相关性。采用Kaplan-Meier对数秩检验和Cox回归风险比分析生存率。
LC肿瘤细胞中IL-12Rβ2表达和TIL比率高于IL-23R表达和TIL比率。在LC组织中,尤其是高分化LC中,IL-12Rβ2和IL-23R表达与TIL比率之间存在显著相关性。此外,肿瘤细胞IL-12Rβ2高表达或IL-23R低表达的生存率分别优于相应的低表达或高表达。IL-12Rβ2比率和IL-23R比率也有类似结果。最后,在所有基因表达组合组中,IL-12Rβ2高表达且IL-23R低表达的患者预后最佳(风险比,0.1;95%可信区间,0.0-0.8)。同样,IL-12Rβ2高表达且IL-23R TIL低阳性率的患者生存率最高(风险比,0.1;95%可信区间,0.0-0.4)。
IL-12Rβ2和IL-23R在肿瘤细胞和TIL之间建立了一种稳态,这种稳态影响预后。虽然IL-12Rβ2和IL-23R的表观遗传免疫编辑的内在机制尚不清楚,但需要更多更大规模的功能研究来验证。