Oncotarget

Research Papers:

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

Hitomi Mori, Makoto Kubo _, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda and Masafumi Nakamura

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Oncotarget. 2017; 8:15584-15592. https://doi.org/10.18632/oncotarget.14698

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Abstract

Hitomi Mori1,*, Makoto Kubo1,*, Rin Yamaguchi2, Reiki Nishimura3, Tomofumi Osako3, Nobuyuki Arima4, Yasuhiro Okumura5, Masayuki Okido6, Mai Yamada1, Masaya Kai1, Junji Kishimoto7, Yoshinao Oda8, Masafumi Nakamura1

1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

2Department of Pathology, Kurume University Medical Center, Kurume, Japan

3Breast Center, Kumamoto Shinto General Hospital, Kumamoto, Japan

4Department of Pathology, Kumamoto Shinto General Hospital, Kumamoto, Japan

5Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto, Japan

6Department of Surgery, Hamanomachi Hospital, Fukuoka, Japan

7Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

8Department 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: [email protected]

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.


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