The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

Abstract

// Hitomi Mori 1, * , Makoto Kubo 1, * , Rin Yamaguchi 2 , Reiki Nishimura 3 , Tomofumi Osako 3 , Nobuyuki Arima 4 , Yasuhiro Okumura 5 , Masayuki Okido 6 , Mai Yamada 1 , Masaya Kai 1 , Junji Kishimoto 7 , Yoshinao Oda 8 , Masafumi Nakamura 1 1 Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 2 Department of Pathology, Kurume University Medical Center, Kurume, Japan 3 Breast Center, Kumamoto Shinto General Hospital, Kumamoto, Japan 4 Department of Pathology, Kumamoto Shinto General Hospital, Kumamoto, Japan 5 Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto, Japan 6 Department of Surgery, Hamanomachi Hospital, Fukuoka, Japan 7 Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan 8 Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan * These authors have contributed equally to this work Correspondence to: Makoto Kubo, email: mkubo@tumor.med.kyushu-u.ac.jp Keywords: programmed cell death ligand-1, tumor-infiltrating lymphocytes, triple-negative breast cancer, biomarker, prognosis Received: August 02, 2016      Accepted: December 27, 2016      Published: January 17, 2017 ABSTRACT 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.