Department Giorgio Segre of Pharmacology, Siena University School of Medicine, Italy.
J Immunother. 2010 May;33(4):435-41. doi: 10.1097/CJI.0b013e3181d32f01.
Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies, like GOLFIG chemoimmunotherapy (gemcitabine, oxaliplatin, 5-fluorouracil/folinic acid, granulocyte macrophage colony-stimulating factor, and aldesleukine), that resulted a safe and very active regimen. Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs, increase of central memory T cells, and decrease of regulatory T cells (Treg) in the peripheral blood. We thus investigated a potential correlation between the Treg tumor infiltration at diagnosis and the clinical outcome in a current randomized phase 3 trial aimed to compare the GOLFIG regimen with the standard FOLFOX chemotherapy (GOLFIG-2). An immunohistochemistry study was carried out to quantify the infiltration of Treg/FoxP3+ T lymphocytes in tumor samples of 57 patients enrolled in the GOLFIG-2 trial. Treg tumor infiltration scores were correlated with overall survival, treatment-relative survival, and progression-free survival (PFS). Higher Treg tumor infiltration scores were associated with a better prognosis in the whole series (Treg high score vs. low score: overall survival=mean 43.2 mo vs. 28.6 mo, P=0.0005) and a better outcome after treatment (Treg high score vs. low score: PFS=mean 15.8 mo vs. 8.8 mo, P=0.0009; treatment-relative survival=mean 23.1 mo vs. 18.2 mo, P=0.004). PFS was significantly longer in GOLFIG high versus all other subgroups (mean 18.1 mo vs. 9.9 mo, P=0.01). Our results suggest that a higher FoxP3+ T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy.
肿瘤免疫反应和化疗诱导的免疫调节是设计新策略的基础，如 GOLFIG 化疗（吉西他滨、奥沙利铂、5-氟尿嘧啶/亚叶酸、粒细胞巨噬细胞集落刺激因子和阿地白介素），这是一种安全且非常有效的方案。GOLFIG 的抗肿瘤活性和免疫反馈与自身免疫迹象、中央记忆 T 细胞增加和外周血调节性 T 细胞（Treg）减少的患者的最佳结果密切相关。因此，我们在一项当前的随机 3 期试验中研究了 Treg 在肿瘤中的浸润与临床结果之间的潜在相关性，该试验旨在比较 GOLFIG 方案与标准 FOLFOX 化疗（GOLFIG-2）。我们进行了一项免疫组织化学研究，以定量分析 57 名入组 GOLFIG-2 试验的患者肿瘤样本中 Treg/FoxP3+T 淋巴细胞的浸润。Treg 肿瘤浸润评分与总生存、治疗相关生存和无进展生存（PFS）相关。在整个系列中，Treg 肿瘤浸润评分越高与预后越好相关（Treg 高评分与低评分：总生存=平均 43.2 个月与 28.6 个月，P=0.0005），治疗后结局越好（Treg 高评分与低评分：PFS=平均 15.8 个月与 8.8 个月，P=0.0009；治疗相关生存=平均 23.1 个月与 18.2 个月，P=0.004）。GOLFIG 高评分组的 PFS 明显长于所有其他亚组（平均 18.1 个月与 9.9 个月，P=0.01）。我们的结果表明，在接受化疗或化疗免疫治疗的结肠癌患者中，更高的 FoxP3+T 淋巴细胞肿瘤浸润评分是一个有利的预后因素。
