Ogiya Rin, Niikura Naoki, Kumaki Nobue, Bianchini Giampaolo, Kitano Shigehisa, Iwamoto Takayuki, Hayashi Naoki, Yokoyama Kozue, Oshitanai Risa, Terao Mayako, Morioka Toru, Tsuda Banri, Okamura Takuho, Saito Yuki, Suzuki Yasuhiro, Tokuda Yutaka
Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
Department of Pathology, School of Medicine, Tokai University, Isehara, Japan.
Cancer Sci. 2016 Dec;107(12):1730-1735. doi: 10.1111/cas.13101.
The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2 , n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8 and CD4 T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2 and TN breast cancers have a lower percentage of TILs and CD8 and CD4 T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.
肿瘤浸润淋巴细胞（TILs）的存在与乳腺癌患者良好的长期预后相关。然而，关于转移进展过程中TILs的变化却知之甚少。为了证实我们的假设，即恶性肿瘤在转移过程中会逃避宿主免疫系统，我们评估了原发性和转移性乳腺肿瘤配对样本中TILs的百分比。我们回顾性地确定了25例于1990年至2009年期间在东海大学医院（日本伊势原）被诊断为人类表皮生长因子受体2（HER2，n = 14）和三阴性（TN，n = 11）早期乳腺癌的患者，这些患者随后经肿瘤活检/切除证实发生了局部或远处复发。对这些配对样本的苏木精-伊红染色切片进行基质TILs评估。使用针对CD4、CD8、Foxp3、程序性细胞死亡配体1（PD-L1）、PD-L2和HLA I类的一抗进行免疫组织化学染色，以对TILs和乳腺肿瘤进行特征描述。原发性肿瘤中TILs的百分比显著高于转移性肿瘤（分别为平均34.6%和平均15.7%）（配对t检验，P = 0.004），并且从原发性肿瘤到转移性肿瘤，CD8和CD4 T细胞的百分比显著下降（配对t检验，分别为P = 0.008和P = 0.026）。从原发性肿瘤到转移性肿瘤，PD-L1、PD-L2和HLA I类抗体表达从阳性变为阴性，反之亦然。与原发性肿瘤相比，HER2和TN乳腺癌首次转移复发时的肿瘤TILs、CD8和CD4 T细胞百分比更低，这表明免疫逃逸在肿瘤进展中起作用。
