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新辅助化疗治疗的腔面B/HER 2阴性乳腺癌患者中CD8肿瘤浸润淋巴细胞的预测和预后意义

Predictive and prognostic significance of CD8 tumor-infiltrating lymphocytes in patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant chemotherapy.

作者信息

Al-Saleh Khalid, Abd El-Aziz Nashwa, Ali Arwa, Abozeed Waleed, Abd El-Warith Ahmed, Ibraheem Ahmed, Ansari Jawaher, Al-Rikabi Ammar, Husain Sufia, Nabholtz Jean-Marc

机构信息

Division of Hematology/Oncology, Department of Medicine, King Khalid University Hospital/College of Medicine, King Saud University, Riyadh 11472 7805, Saudi Arabia.

Department of Medical Oncology, South Egypt Cancer Institute, Assiut University, Assiut 71516, Egypt.

出版信息

Oncol Lett. 2017 Jul;14(1):337-344. doi: 10.3892/ol.2017.6144. Epub 2017 May 10.

Abstract

The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8 tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8(CD8) TIL in patients with luminal BC. The present study aimed to evaluate the predictive and prognostic significance of CD8 TIL in patients with luminal B/human epidermal growth factor receptor 2 (HER 2)-negative BC treated with anthracycline-based neoadjuvant chemotherapy (NC). A total of 31 patients who underwent breast-conserving surgery or mastectomy post-NC were enrolled. Immunostaining for CD8 TIL was performed using rabbit monoclonal antibodies against human CD8. Intra- and peritumoral CD8 TIL expression levels were classified into high and low, based on the median value of each. CD8 TIL expression data were demonstrated to be correlated with disease-free survival (DFS) and overall survival (OS), using Kaplan-Meier and Cox's proportional hazards regression tests. The results revealed that, among all clinicopathological characteristics, only pathological complete response (pCR) was significantly correlated with intratumoral CD8 TIL expression (P=0.016). A total of 9/16 patients (56%) with high intratumoral CD8 TIL expression achieved pCR, in contrast with 2 out of 15 patients (13.3%) with low expression (P=0.016). High expression of intratumoral CD8 TIL was significantly associated with OS (log-rank test, P=0.023). Multivariate Cox regression analysis revealed that intratumoral expression of CD8 TIL was an independent prognostic factor for OS [hazard ratio (HR)=2.82; 95% confidence interval (CI)=0.911-4.833, P=0.007], but not for DFS (HR=1.11; 95% CI=0.282-2.078; P=0.508). In conclusion, the results of the present study suggested that high intratumoral CD8 TIL expression was significantly predictive of pCR post-NC, and represented an independent prognostic factor for improved OS. In contrast, low intratumoral CD8 TIL expression was a strong predictor of lack of pCR to NC, as well as an independent prognostic factor for poor OS. Assessment of the immune response in conjunction with the usual parameters may aid in the further stratification of patients with luminal B/HER 2-negative BC regarding the prediction of pCR post-NC and overall prognosis.

摘要

包括管腔癌在内的乳腺癌(BC)亚型的免疫生物学仍不清楚。分化簇(CD)8肿瘤浸润淋巴细胞(TIL)是肿瘤特异性细胞适应性免疫的重要组成部分。然而,仅有少数研究探讨了分化簇8(CD8)TIL在管腔型BC患者中的意义。本研究旨在评估CD8 TIL在接受蒽环类药物新辅助化疗(NC)的管腔B/人表皮生长因子受体2(HER 2)阴性BC患者中的预测和预后意义。总共纳入了31例在NC后接受保乳手术或乳房切除术的患者。使用抗人CD8兔单克隆抗体对CD8 TIL进行免疫染色。根据各自的中位数,将肿瘤内和肿瘤周围CD8 TIL表达水平分为高和低。使用Kaplan-Meier和Cox比例风险回归检验证明CD8 TIL表达数据与无病生存期(DFS)和总生存期(OS)相关。结果显示,在所有临床病理特征中,仅病理完全缓解(pCR)与肿瘤内CD8 TIL表达显著相关(P = 0.016)。肿瘤内CD8 TIL表达高的16例患者中有9例(56%)达到pCR,相比之下,表达低的15例患者中有2例(13.3%)达到pCR(P = 0.016)。肿瘤内CD8 TIL高表达与OS显著相关(对数秩检验,P = 0.023)。多变量Cox回归分析显示,肿瘤内CD8 TIL表达是OS的独立预后因素[风险比(HR)= 2.82;95%置信区间(CI)= 0.911 - 4.833,P = 0.007],但不是DFS的独立预后因素(HR = 1.11;95% CI = 0.282 - 2.078;P = 0.508)。总之,本研究结果表明,肿瘤内CD8 TIL高表达对NC后的pCR具有显著预测性,并且是OS改善的独立预后因素。相反,肿瘤内CD8 TIL低表达是NC后缺乏pCR的有力预测指标,也是OS不良的独立预后因素。结合常规参数评估免疫反应可能有助于对管腔B/HER 2阴性BC患者在预测NC后pCR和总体预后方面进行进一步分层。

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