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

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

doi:10.18632/oncotarget.14698

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.

Highlights

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and represents up to 20% of all breast cancers
Our findings suggest that PDL1-positive/tumor-infiltrating lymphocytes (TILs)-low tumors are associated with a poor prognosis in patients with triple-negative breast cancer (TNBC), and that it is important to focus on the combination of programmed cell death ligand-1 (PD-L1) expression on tumor cells and TILs present in the tumor microenvironment
The nuclear grade and Ki-67 index were higher in PD-L1-positive tumors than in PD-L1-negative tumors (P = 0.0015 and P < 0.0001, respectively), there was no significant difference between the two groups with respect to tumor size, nodal status and pathological stage (Table 1)

Summary

Introduction

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and represents up to 20% of all breast cancers. This subtype is a heterogeneous tumor that encompasses other breast cancer molecular subtypes. In TNBC in particular, a high number of stromal TILs is predictive of a more favorable outcome, and the prognostic value of stromal TILs can be considered strong evidence. According to the International TILs Working Group, TILs should not yet be used as a biomarker for withholding chemotherapy [8]

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Results

Conclusion