J Cancer 2020; 11(24):7246-7252. doi:10.7150/jca.50441

Research Paper

Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome

Mineui Hong1, Jeong Won Kim1, Min kyoon Kim2, Bong wha Chung3, Soo kyung Ahn3✉

1. Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-ku, Seoul, 07441, Korea
2. Department of Surgery, College of Medicine, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Korea
3. Department of Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-ku, Seoul, 07441, Korea

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Citation:
Hong M, Kim JW, Kim Mk, Chung Bw, Ahn Sk. Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome. J Cancer 2020; 11(24):7246-7252. doi:10.7150/jca.50441. Available from https://www.jcancer.org/v11p7246.htm

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Abstract

Purpose: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in antitumor immune responses. However, there is considerable inconsistency regarding the prognostic value of PD-L1 expression status in breast cancer. We sought to evaluate the differential prognostic impacts of tumoral versus stromal immune cell PD-L1 expression in primary breast cancer.

Materials & Methods: Both tumoral and stromal immune PD-L1 expression in formalin-fixed, paraffin-embedded tumor samples from 233 breast cancer patients without initial stage IV metastases were evaluated by immunohistochemistry using a mouse monoclonal anti-PDL1 antibody. Clinicopathological variables were also documented. A Cox regression model was used to assess the association of tumoral/stromal immune PD-L1 expression with clinical outcome using disease-free survival (DFS) as the primary end point.

Results: Both tumoral and stromal immune PD-L1 expression were associated with aggressive tumor characteristics, including higher histologic grade, as well as negative estrogen receptor, negative progesterone receptor, and positive human epithelial growth factor receptor 2 (HER2) status Multivariate analyses further demonstrated that stromal immune cell, but not tumoral, PD-L1 expression was a favorable prognostic factor for survival.

Conclusions: Despite its association with aggressive tumor features, PD-L1 expression on stromal immune cells emerged as a positive prognostic biomarker in breast cancer. This pro-survival effect might reflect the presence of a strong antitumor immune response that leads to PD-L1 expression.

Keywords: PD-L1, breast cancer, prognosis, immune-oncology, stromal immune cells