Institute of Respiratory Diseases of Sun Yat-Sen University, Division of Pulmonary and Critical Care, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Street, Guangzhou 510630, China.
Cancer Immunol Immunother. 2012 Oct;61(10):1849-56. doi: 10.1007/s00262-012-1231-7. Epub 2012 Mar 29.
Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.
越来越多的临床前证据表明，抗肿瘤免疫反应有助于化疗的成功。肿瘤浸润淋巴细胞（TILs）对新辅助化疗治疗非小细胞肺癌（NSCLC）反应的预测意义尚不清楚。本研究旨在探讨 TIL 亚型在接受铂类化疗的晚期 NSCLC 患者中的预后和预测价值。共回顾性纳入 159 例 III 期和 IV 期 NSCLC 患者。采用免疫组织化学法检测化疗前肿瘤组织中 CD3(+)、CD4(+)、CD8(+)和 Foxp3(+)TIL 的发生率。采用中位数作为截断值，将 TIL 亚群密度视为二分类变量。采用 Kaplan-Meier 法估计生存曲线，对数秩检验比较各组间总生存期的差异。采用 Cox 回归分析评估 TIL 亚群密度的预后作用。CD3(+)、CD4(+)、CD8(+)和 FOXP3(+)TIL 的存在与任何临床病理特征均无关。TIL 存在与否以及联合分析在 Cox 回归模型中对总生存期均无明显预后作用。相反，肿瘤部位较高的 FOXP3(+)/CD8(+)比值是总体队列中对铂类化疗反应不良的独立因素。这些发现表明，肿瘤微环境中免疫性 CD8(+)和 FOXP3(+)Treg 细胞浸润是预测晚期 NSCLC 患者接受铂类新辅助化疗反应的一个因素。对微环境免疫状态的临床相关性的理解可能为癌症免疫治疗的新策略设计提供重要线索。
