Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.
Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.
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DOI：
10.1158/2326-6066.cir-15-0110
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发表时间：
2016-05
影响因子：
10.1
通讯作者：
He AR
中科院分区：
文献类型：
--
作者：
Gabrielson A;Wu Y;Wang H;Jiang J;Kallakury B;Gatalica Z;Reddy S;Kleiner D;Fishbein T;Johnson L;Island E;Satoskar R;Banovac F;Jha R;Kachhela J;Feng P;Zhang T;Tesfaye A;Prins P;Loffredo C;Marshall J;Weiner L;Atkins M;He AR
浸润肿瘤的免疫细胞可能是手术切除的肝细胞癌（HCC）患者的预后因素。肿瘤内总（CD 3+）和细胞毒性（CD 8+）T淋巴细胞的密度在肿瘤内部和65个阶段I至IV HCC组织标本的侵袭性边缘从一个单一的队列进行了测量。将内部和边缘的免疫细胞密度转换为二进制评分（0，低; 1，高），这与肿瘤复发和无复发生存期（RFS）相关。此外，程序性死亡1（PD-1）和程序性死亡配体1（PD-L1）的表达与CD 3+和CD 8+细胞密度和临床结局相关。内部和边缘的高密度CD 3+和CD 8 + T细胞沿着相应的免疫评分与低复发率（P=0.007）和延长的无复发生存期（RFS）（P = 0.002）显著相关。在校正血管浸润和细胞分化的多变量logistic回归模型中，CD 3+和CD 8+细胞密度均预测复发，CD 3+和CD 8+的比值比分别为5.8（95%CI 1.6-21.8）和3.9（95%CI 1.1-14.1）。PD-L1染色阳性与高CD 3和CD 8密度相关（分别为P = 0.024和0.005），并预测复发率较低（P = 0.034），以及RFS延长（P = 0.029）。因此，免疫评分和PD-L1表达是接受原发性肿瘤切除术的HCC患者的有用预后标志物。
Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding immunoscores, were significantly associated with a low rate of recurrence (P=0.007) and a prolonged relapse-free survival (RFS) (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 (95% CI 1.6-21.8) for CD3+, and 3.9 (95% CI 1.1-14.1) for CD8+. Positive PD-L1 staining correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively), and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection.