Multispectral quantitative immunohistochemical analysis of tumor-infiltrating lymphocytes in relation to programmed death-ligand 1 expression in triple-negative breast cancer

Tomoharu Sugie, Eiichi Sato, Minoru Miyashita, Rin Yamaguchi, Takashi Sakatani, Yuji Kozuka, Suzuko Moritani, Eiji Suzuki, Kazuhiro Kakimi, Yoshiki Mikami, Takuya Moriya

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Programmed death-ligand 1 (PD-L1) expression on immune cells (ICs) is a predictive marker for PD-L1 checkpoint blockade in patients with triple-negative breast cancer (TNBC). However, the level of PD-L1 expression and the percentage of cells that are PD-L1+ are continuous variables not dichotomous variables for tumor-infiltrating lymphocytes (TILs) and other cells. Methods: Multiplexed immunohistochemistry was applied to 31 archived surgical specimens from untreated TNBC patients. TIL levels were visually scored, and CD8+ T cells and PD-L1+ ICs were quantified using an automated multispectral imaging system. PD-L1 expression was assessed within a multiplexed context (CD8 combined spectral composite). Results: The mean value of stromal TILs (i.e., the percentage of the stromal area with a dese mononuclear infiltrate) was 20%. The frequency of patients with PD-L1-positive tumor cells (TC) and ICs was 38.7% and 32.2%, respectively, with a significant association between them. TIL levels were correlated with CD8+ T cell infiltration in the stroma (Spearman r = 0.795, p < 0.0001). PD-L1 expression on IC was significantly associated with TIL levels (Spearman r = 0.790, p < 0.001) and infiltration of CD8+ T cells (Spearman r = 0.683, p < 0.0001). Conclusions: The level of PD-L1 on IC was correlated with the level of PD-L1 on TC as well as TIL levels and infiltration of CD8+ T cells. These results suggest that high PD-L1 on IC may reflect T cell-inflamed tumors with the amount of TILs present, including the CD8+ T cells required for anti-tumor responses.

Original languageEnglish
Pages (from-to)519-526
Number of pages8
JournalBreast Cancer
Volume27
Issue number4
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • Breast cancer
  • Multiplex immunohistochemistry
  • Programmed death-ligand 1
  • Triple-negative
  • Tumor-infiltrating lymphocyte

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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