T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival.
T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival.
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DOI：
10.1038/bjc.2011.261
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发表时间：
2011-07-26
影响因子：
8.8
通讯作者：
Ghiringhelli, F.
中科院分区：
文献类型：
--
作者：
Ladoire, S.;Arnould, L.;Mignot, G.;Apetoh, L.;Rebe, C.;Martin, F.;Fumoleau, P.;Coudert, B.;Ghiringhelli, F.
在her2过表达的乳腺癌中，越来越多的临床前证据表明，一些化疗，如曲妥珠单抗，以及紫杉烷，能够触发T辅助1 （Th1）抗癌免疫反应，有助于治疗成功。辅助T细胞1免疫反应的特征是转录因子T-bet在CD4 T淋巴细胞中的表达。我们假设在新辅助化疗后肿瘤免疫浸润中存在这种T细胞可以预测患者的生存。我们对102例连续接受蒽环类或紫杉烷联合曲妥珠单抗新辅助化疗的her2过表达乳腺癌患者进行了免疫组化研究，研究了两组患者化疗前后肿瘤周围T-bet+淋巴细胞浸润情况。采用Kaplan-Meier分析和Cox模型评估无复发生存期（RFS）。58例患者接受曲妥珠单抗-紫杉烷治疗，44例患者接受基于蒽环类药物的新辅助化疗。化疗后肿瘤周围淋巴组织中T-bet+淋巴细胞的出现在曲妥珠单抗-紫杉烷治疗的患者中更为频繁（P=0.0008）。中位随访40个月后，仅在曲妥珠单抗-紫杉烷治疗的患者中，新辅助化疗后T-bet+淋巴细胞的存在赋予了显著更好的RFS （log-rank检验P=0.011）。在该人群中，多变量Cox回归模型显示，新辅助化疗后肿瘤周围淋巴组织中仅存在T-bet+淋巴细胞与RFS改善独立相关（P=0.04）。这些发现表明，新辅助曲妥珠单抗-紫杉烷治疗后T-bet+ Th1淋巴细胞的浸润可能是her2过表达乳腺癌预后改善的一个新的独立预后因素。
In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival. In a series of 102 consecutive HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy incorporating antracyclines or taxane and trastuzumab, we studied by immunohistochemistry the peritumoral lymphoid infiltration by T-bet+ lymphocytes before and after chemotherapy in both treatment groups. Kaplan–Meier analysis and Cox modelling were used to assess relapse-free survival (RFS). Fifty-eight patients have been treated with trastuzumab–taxane and 44 patients with anthracyclines-based neoadjuvant chemotherapy. The presence of T-bet+ lymphocytes in peritumoral lymphoid structures after chemotherapy was significantly more frequent in patients treated with trastuzumab–taxane (P=0.0008). After a median follow-up of 40 months, the presence of T-bet+ lymphocytes after neoadjuvant chemotherapy confers significantly better RFS (log-rank test P=0.011) only in patients treated with trastuzumab–taxane. In this population, multivariate Cox regression model showed that only the presence of T-bet+ lymphocytes in peritumoral lymphoid structures after neoadjuvant chemotherapy was independently associated with improved RFS (P=0.04). These findings indicate that the tumour infiltration by T-bet+ Th1 lymphocytes following neoadjuvant trastuzumab–taxane may represent a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma.
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DOI：
10.1084/jem.177.4.1199
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Manetti R;Parronchi P;Giudizi MG;Piccinni MP;Maggi E;Trinchieri G;Romagnani S
通讯作者：
Romagnani S
影响因子：
11.5
作者：
Roepman, Paul;Jassem, Jacek;van Zandwijk, Nico
通讯作者：
van Zandwijk, Nico
影响因子：
45.3
作者：
Untch, Michael;Rezai, Mahdi;von Minckwitz, Gunter
通讯作者：
von Minckwitz, Gunter
影响因子：
15.9
作者：
Parihar, R;Dierksheide, J;Carson, WE
通讯作者：
Carson, WE
影响因子：
15.3
作者：
Dhodapkar, KM;Krasovsky, J;Dhodapkar, MV
通讯作者：
Dhodapkar, MV