Predictive factors of the tumor immunological microenvironment for long-term follow-up in early stage breast cancer.
Predictive factors of the tumor immunological microenvironment for long-term follow-up in early stage breast cancer.
复制标题
早期乳腺癌长期随访中肿瘤免疫微环境的预测因素。
DOI：
10.1111/cas.13114
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发表时间：
2017-01
期刊：
影响因子：
5.7
通讯作者：
Akagi Y
中科院分区：
文献类型：
--
作者：
Okabe M;Toh U;Iwakuma N;Saku S;Akashi M;Kimitsuki Y;Seki N;Kawahara A;Ogo E;Itoh K;Akagi Y
本研究旨在探讨乳腺癌肿瘤环境中免疫因素的相关性，采用免疫组织化学染色方法检测程序性死亡1/程序性死亡配体1（programmed death 1/programmed death ligand 1，PDL 1）的表达（PD-1/PD-L1）、磷酸酶和张力蛋白同源物（PTEN）、肿瘤浸润淋巴细胞（TIL）和巨噬细胞，分析免疫因素与早期乳腺癌（EBC）患者临床预后的关系。共调查了97例接受标准手术的EBC患者。通过免疫组织化学分析评估PD-1/PD-L1和PTEN的表达以及CD 3 + TIL、CD 8 + TIL和CD 163+巨噬细胞的密度。统计分析免疫因素与临床结局的关系。在三阴性乳腺癌病例中，CD 3 + TIL、CD 8 + TIL和CD 163+巨噬细胞的密度以及PTEN的非表达显著更高。CD 8 + TIL密度和CD 8 +/PD-L1+表达是无病生存期和总生存期（OS）的预测因素。与无PTEN表达（P = 0.049）和有PD-L1表达（P = 0.036）的患者相比，有PTEN表达的人表皮生长因子2（HER 2）阳性患者和无PD-L1表达的luminal/HER 2阴性患者的OS显著更长。此外，与无PD-L1 +/CD 8+表达的患者相比，有PD-L1 +/CD 8+表达的患者的中位无进展生存期（P = 0.022）和中位OS（P = 0.037）更差。CD 3 + TILs、CD 8 + TILs和CD 163+巨噬细胞浸润EBC的肿瘤区域。特别是，三阴性乳腺癌在肿瘤环境中具有较高的TIL浸润率。PTEN表达和PD-L1表达缺失分别与HER 2阳性和Luminal/HER 2阴性EBC患者的良好生存相关。PD-L1表达结合CD 8+密度与侵袭性临床结局显著相关。
The aim of this research was to investigate the correlation of immunologic factors in the tumor environment of breast cancer, using immunohistological staining to evaluate the expression of programmed death 1/programmed death ligand 1 (PD‐1/PD‐L1), phosphatase and tensin homolog (PTEN), tumor infiltrating lymphocytes (TILs), and macrophages, and to analyze the association between the immunologic factors and clinical outcome for patients with early stage breast cancer (EBC). A total of 97 EBC patients who underwent standard surgery were investigated. Expression of PD‐1/PD‐L1 and PTEN and the density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages were evaluated by immunohistochemical analysis. The association between the immunologic factors and clinical outcome was statistically analyzed. The density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages and non‐expression of PTEN was significantly higher in cases of triple negative breast cancer. CD8+ TIL density and CD8+/PD‐L1+ expression were predictive factors for disease‐free survival and overall survival (OS). Human epidermal growth factor 2 (HER2)‐positive patients with PTEN expression and luminal/HER2‐negative patients without PD‐L1 expression had significantly longer OS compared to patients without PTEN expression (P = 0.049) and with PD‐L1 expression (P = 0.036), respectively. Furthermore, patients with PD‐L1+/CD8+ expression had worse median progression‐free survival (P = 0.022) and median OS (P = 0.037) compared with patients without PD‐L1+/CD8+ expression. The CD3+ TILs, CD8+ TILs, and CD163+ macrophages were shown to infiltrate the tumor area of EBC. In particular, triple negative breast cancer had a higher rate of TIL infiltration within the tumor environment. Expression of PTEN and lack of PD‐L1 expression were associated with favorable survival in HER2‐positive and luminal/HER2‐negative EBC patients, respectively. The PD‐L1 expression combined with CD8+ density was significantly associated with an aggressive clinical outcome.