Mori Hitomi, Kubo Makoto, Yamaguchi Rin, Nishimura Reiki, Osako Tomofumi, Arima Nobuyuki, Okumura Yasuhiro, Okido Masayuki, Yamada Mai, Kai Masaya, Kishimoto Junji, Oda Yoshinao, Nakamura Masafumi
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Pathology, Kurume University Medical Center, Kurume, Japan.
Oncotarget. 2017 Feb 28;8(9):15584-15592. doi: 10.18632/oncotarget.14698.
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies.
本研究纳入了2004年1月至2014年12月期间接受手术切除且未接受新辅助化疗的原发性三阴性乳腺癌(TNBC)患者。在研究的248例TNBC中,103例(41.5%)肿瘤检测到程序性细胞死亡配体-1(PD-L1)表达,118例(47.6%)肿瘤存在高水平的肿瘤浸润淋巴细胞(TILs)。PD-L1表达与高水平的TILs相关,但不是一个预后因素。TILs高的肿瘤患者的总生存期优于TILs低的肿瘤患者(P = 0.016)。PD-L1表达与TILs之间存在强烈的相互作用,这与无复发生存期(P = 0.0018)和总生存期(P = 0.015)均相关。多变量Cox比例风险模型分析显示,PD-L1阳性/TILs低是无复发生存期和总生存期的独立负性预后因素。我们的研究结果表明,PD-L1阳性/TILs低的肿瘤与TNBC患者的不良预后相关,关注肿瘤细胞上PD-L1表达与肿瘤微环境中存在的TILs的组合很重要。这些生物标志物可能有助于TNBC的分层、预测预后以及开发新的癌症免疫疗法。