Expression of PD-L1 Attenuates the Positive Impacts of High-level Tumor-infiltrating Lymphocytes on Prognosis of Triple-negative Breast Cancer

Cancer Biol Ther. 2019;20(8):1105-1112. doi: 10.1080/15384047.2019.1595282. Epub 2019 Mar 31.


Background: Among all breast cancer subtypes, triple-negative breast cancer (TNBC) has aggressive clinical manifestations including more frequent relapses and metastases. The roles of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in TNBC clinicopathological behaviors and patients' survival outcomes remain unclear. Methods: TNBC (108 cases) patients with at least 5-year follow-up were analyzed for PD-L1 expression and TILs by immunohistochemistry. We also analyzed the relationships between PD-L1 expression, TILs and clinicopathological characteristics. Furthermore, we explored the effect of PD-L1 expression and TILs on prognosis as illustrated by disease-free survival (DFS). Results: The expression of PD-L1 was related to more aggressive clinicopathological behaviors in TNBC patients including a larger tumor size, higher incidence of PL-1-ALN, more frequent distant metastasis, and a reduced disease-free survival. In contrast, patients with high-level TILs showed less aggressive disease progression hence a better prognosis compared to patients with low-level TILs. Among patients with high-level TILs, PD-L1 expression was correlated with adverse prognosis. Conclusions: Expression of PD-L1 and low-level TILs in TNBC patients were associated with adverse clinical outcomes. However, the positive impact of high-level TILs was attenuated by PD-L1 expression. Our results suggest potential biomarkers for a selection of indicated cases in the TNBC patients for anti-PD-L1/anti-PD1 immunotherapy.

Keywords: PD-L1; TILs; TNBC; immunotherapy; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor*
  • Combined Modality Therapy
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / immunology*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Microenvironment


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human

Grants and funding

This work was supported by the China Medical University Major Construction Project (No. 2017ZDZX05), National Natural Science Foundation of China (81572609 and 81872159), Liaoning Colleges Innovative Talent Support Program (Name: Cancer Stem Cell Origin and Biological Behavior), and Liaoning Province College Student Innovation Training Project (201810159068).