Use of Tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer.
Use of Tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer.
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DOI：
10.1371/journal.pone.0170634
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ohira M
中科院分区：
文献类型：
--
作者：
Kashiwagi S;Asano Y;Goto W;Takada K;Takahashi K;Noda S;Takashima T;Onoda N;Tomita S;Ohsawa M;Hirakawa K;Ohira M
目前，甲磺酸eribuin(Eribuin)被用于治疗局部晚期或转移性乳腺癌(MBC)。它是一种细胞毒剂，具有独特的抑制癌细胞上皮-间充质转化(EMT)的机制。另一方面，肿瘤浸润性淋巴细胞(TIL)被认为是免疫反应监测的指标，已被报道为预后因素和治疗效果的预测因子。我们认为具有EMT抑制机制的eriBulin可能通过改善免疫微环境而产生抗肿瘤作用，本研究以TIL为标志物，探讨了乳腺癌eribuin化疗对免疫微环境的影响。对52例接受淫羊藿苷化疗的MBC患者的TIL进行了检测。回顾分析按标准方法评估的TIL与预后的关系，包括Eribuin化疗的疗效。52例MBC患者中，高TIL组29例(55.8%)，低TIL组23例(44.2%)。与低TIL组相比，高TIL组的三阴性乳腺癌(TNBC)显著增多(p=0.008)。在结果分析中，高TIL组的TNBC患者的无病生存期显著长于低TIL组的患者(p=0.033，LOG-RANK)，但在所有乳腺癌患者(P=0.489，LOG-RANK)或非TNBC患者(P=0.878，LOG-RANK)中没有显著差异。在对TNBC患者复发的多因素分析中，高TIL组再次成为预后良好的独立因素(p=0.031，HR=0.063)。本研究结果提示TIL可作为预测Eribuin化疗对TNBC疗效的有用指标。
Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker. TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively. Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063). The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.