Tumor Infiltrating Lymphocytes and CD8+T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma

Tumor Infiltrating Lymphocytes and CD8+T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma
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DOI:
10.1007/s12105-019-01101-6
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发表时间:
2019-11-20
影响因子:
2.1
通讯作者:
Fountzilas, Georgios
Fountzilas, Georgios
中科院分区:
其他
文献类型:
--
作者:
Chatzopoulos, Kyriakos;Kotoula, Vassiliki;Fountzilas, Georgios

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为探讨肿瘤浸润淋巴细胞(TIL)和CD 8 + T细胞亚群在喉鳞状细胞癌(LSCC)患者中的预后意义,对283例LSCC患者进行了检测。在整个切片上对TIL密度进行形态学评估。在每个肿瘤的多个组织微阵列核心上评估CD 8+细胞计数/mm(2)(高/低CD 8 +/mm(2)的中位数计数)。TIL密度和CD 8+计数彼此弱相关(斯皮尔曼rho = 0.348)。在28%的肿瘤中显示出异质性CD 8+计数/mm 2。在单变量分析中,观察到CD 8表达和淋巴结状态之间的显著相互作用;在淋巴结阳性患者中,与低CD 8+肿瘤患者相比,高CD 8+肿瘤患者复发风险降低77%(相互作用p < 0.001),死亡风险降低74%(相互作用p = 0.002)。在多变量分析中,较高的TIL密度独立地赋予整个队列中较低的复发风险(HR 0.87; 95% CI 0.77-0.98; Wald's p = 0.017)和淋巴结阳性患者(HR 0.41; 95% CI 0.23-0.75; p = 0.003),死亡(分别为p = 0.025和p = 0.003)。在任何分析背景下,高CD 8+均不是显著的独立预后标志物。与形态学评估的TIL密度相比,CD 8+浸润的评估似乎不能提供额外的预后信息。也似乎较高的TIL密度和CD 8+浸润的有利预后影响主要涉及淋巴结阳性而不是淋巴结阴性疾病。如果在较大的淋巴结阳性队列中得到验证,这些发现值得考虑用于喉鳞状细胞癌免疫细胞浸润的诊断发展。
To evaluate the prognostic significance of tumor infiltrating lymphocytes (TILs) and of CD8+ T-cell subsets in patients with surgically treated laryngeal squamous cell carcinoma (LSCC), LSCC from 283 patients were examined. TIL density was morphologically assessed on whole sections. CD8+ cell counts/mm(2) were evaluated on multiple tissue microarray cores per tumor (median counts for high/low CD8+/mm(2)). TIL density and CD8+ counts weakly correlated with each other (Spearman's rho = 0.348). Heterogeneous CD8+ counts/mm(2) were demonstrated in 28% of the tumors. In univariate analysis, a significant interaction was observed between CD8 expression and nodal status with respect to outcome; in node-positive patients, those with high CD8+ tumors had 77% lower risk of relapse (interaction p < 0.001) and 74% lower risk for death (interaction p = 0.002) compared to patients with low CD8+ tumors. In multivariate analysis, higher TIL density independently conferred lower risk for relapse in the entire cohort (HR 0.87; 95% CI 0.77-0.98; Wald's p = 0.017) and in node-positive patients (HR 0.41; 95% CI 0.23-0.75; p = 0.003) and, similarly, for death (p = 0.025 and p = 0.003, respectively). High CD8+ was not a significant independent prognostic marker in any analysis setting. The assessment of CD8+ infiltrates does not seem to offer additional prognostic information over the morphologically assessed TIL density. It also appears that the favorable prognostic impact of higher TIL density and CD8+ infiltrates mostly concerns node-positive but not node-negative disease. If validated in larger node-positive cohorts, these findings are worth considering for the diagnostic development of immune cell infiltrates in LSCC.