Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy.
Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy.
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DOI：
10.1097/cji.0b013e3181d32f01
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发表时间：
2010-05
期刊：
影响因子：
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通讯作者：
Tagliaferri P
中科院分区：
文献类型：
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作者：
Correale P;Rotundo MS;Del Vecchio MT;Remondo C;Migali C;Ginanneschi C;Tsang KY;Licchetta A;Mannucci S;Loiacono L;Tassone P;Francini G;Tagliaferri P
结肠癌患者的抗肿瘤免疫应答和化疗诱导的免疫调节代表了设计新策略的基本原理，如GOLFIG化学免疫治疗（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细胞），这产生了一种安全且非常有效的方案。抗肿瘤活性和对GOLFIG的免疫反馈与在具有自身免疫体征、中枢记忆T细胞增加和外周血中调节性T细胞（Treg）减少的患者中观察到的最佳结果严格相关。因此，我们研究了诊断时Treg肿瘤浸润与当前随机III期试验中临床结局之间的潜在相关性，该试验旨在比较GOLFIG方案与标准FOLFOX化疗（GOLFIG-2）。进行免疫组织化学研究以量化在GOLFIG-2试验中招募的57名患者的肿瘤样品中Treg/FoxP 3 + T淋巴细胞的浸润。Treg肿瘤浸润评分与总生存期、治疗相对生存期和无进展生存期（PFS）相关。在整个系列中，Treg肿瘤浸润评分越高，预后越好（Treg高评分vs.低评分：总生存期=平均43.2个月vs. 28.6个月，P = 0.0005）和治疗后更好的结局（Treg高分与低分：PFS =平均15.8个月与8.8个月，P = 0.0009;治疗相对生存期=平均23.1个月与18.2个月，P = 0.004）。GOLFIG高剂量组的PFS显著长于所有其他亚组（平均18.1个月vs. 9.9个月，P = 0.01）。我们的研究结果表明，较高的FoxP 3 + T淋巴细胞肿瘤浸润评分是一个有利的预后因素，结肠癌患者进行化疗或化学免疫治疗。
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.