Nejati Reza, Goldstein Jennifer B, Halperin Daniel M, Wang Hua, Hejazi Nazila, Rashid Asif, Katz Matthew H, Lee Jeffrey E, Fleming Jason B, Rodriguez-Canales Jaime, Blando Jorge, Wistuba Ignacio I, Maitra Anirban, Wolff Robert A, Varadhachary Gauri R, Wang Huamin
From the Departments of *Pathology, †Gastrointestinal Medical Oncology, ‡Surgical Oncology, and §Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Pancreas. 2017 Oct;46(9):1180-1187. doi: 10.1097/MPA.0000000000000914.
The aim of this study was to examine tumor-infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy.
Intratumoral CD4, CD8, and FOXP3 lymphocytes were examined by immunohistochemistry using a computer-assisted quantitative analysis in 136 PDAC patients who received neoadjuvant therapy and pancreaticoduodenectomy. The results were correlated with clinicopathological parameters and survival.
High CD4 TILs in treated PDAC were associated with high CD8 TILs (P = 0.003), differentiation (P = 0.04), and a lower frequency of recurrence (P = 0.02). Patients with high CD4 TILs had longer disease-free survival and overall survival (OS) than did patients with low CD4 TILs (P < 0.01). The median OS of patients with a high CD8/FOXP3 lymphocyte ratio (39.5 [standard deviation, 6.1] months) was longer than that of patients with a low CD8/FOXP3 lymphocyte ratio (28.3 [standard deviation, 2.3] months; P = 0.01). In multivariate analysis, high CD4 TILs were an independent prognostic factor for disease-free survival (hazard ratio, 0.49; 95% confidence interval, 0.30-0.81; P = 0.005) and OS (hazard ratio, 0.54; 95% confidence interval, 0.33-0.89; P = 0.02).
High level of CD4 lymphocytes is associated with tumor differentiation and lower recurrence and is an independent prognostic factor for survival in PDAC patients treated with neoadjuvant therapy.
本研究旨在检测新辅助治疗后胰腺导管腺癌（PDAC）患者的肿瘤浸润淋巴细胞（TILs）及其预后价值。
采用计算机辅助定量分析的免疫组织化学方法，检测136例接受新辅助治疗及胰十二指肠切除术的PDAC患者瘤内的CD4、CD8和FOXP3淋巴细胞。将结果与临床病理参数及生存率进行关联分析。
接受治疗的PDAC患者中，高CD4 TILs与高CD8 TILs相关（P = 0.003）、与分化相关（P = 0.04），且复发频率较低（P = 0.02）。高CD4 TILs患者的无病生存期和总生存期（OS）长于低CD4 TILs患者（P < 0.01）。CD8/FOXP3淋巴细胞比率高的患者的中位OS（39.5 [标准差，6.1]个月）长于CD8/FOXP3淋巴细胞比率低的患者（28.3 [标准差，2.3]个月；P = 0.01）。在多变量分析中，高CD4 TILs是无病生存期（风险比，0.49；95%置信区间，0.30 - 0.81；P = 0.005）和OS（风险比，0.54；95%置信区间，0.33 - 0.89；P = 0.02）的独立预后因素。
高水平的CD4淋巴细胞与肿瘤分化及较低复发相关，是接受新辅助治疗的PDAC患者生存的独立预后因素。
