Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value

Young Keum Kim,Gyungyub Gong,Kyung Un Choi,Chang Hun Lee,Do Youn Park,Ahrong Kim,Won Young Park,Gi Yeong Huh,Jee Yeon Kim,So Jeong Lee

doi:10.1038/s41598-017-11905-7

Abstract

Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0.001, both). High PD-L1 immunoscore in TILs and high total immunoscore (in tumour cells and TILs) of PD-L1 were correlated with high histologic grade (p = 0.001 and p < 0.001, respectively), absence of lymphovascular invasion (p = 0.012 and p = 0.007, respectively), negative hormone receptor expression (p = 0.044 and p = 0.001, respectively) and high TILs level (p < 0.001, both). High PD-L1 mRNA expression was associated with high TILs level (p < 0.001, both). PD-L1 positivity in tumour cells was associated with better disease-free survival in HR−/HER2+ breast cancer (p = 0.039). PD-L1 expression in tumour cells and TILs are significantly associated with TILs level in HER2-positive breast cancer. PD-L1 expression in tumour cells might be positive prognostic factor in HR−/HER2+ breast cancers.

Highlights

Recent progress in the field of immunology supports the theory that the immune system has a role in cancer development through “cancer immunoediting”
In addition to the progress made in immunotherapy and cancer immunology, Teng et al.[21] classified cancers based on tumour infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) expression and proposed immunotherapeutic strategies according to their classification
The programmed death -1 (PD-1) pathway is activated upon engagement of its ligands, PD-L1 or PD-L2, and can modulate T cell activity in several ways

Summary

Introduction

Recent progress in the field of immunology supports the theory that the immune system has a role in cancer development through “cancer immunoediting”. Immune checkpoint blocking agents targeting the cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed death -1 (PD-1)/programmed death-ligand 1 (PD-L1) axis have been developed and possess notable clinical efficacy[5,6,7,8,9,10,11,12,13]. A high level of TILs is associated with a better response to trastuzumab, and is a good prognostic factor in HER2-positive breast cancers[18, 19]. The synergistic effect of anti-PD-1 agent on trastuzumab therapy was demonstrated in HER2-positive breast cancer[17]. Despite efforts to establish a combination therapy involving trastuzumab and anti-PD-1/PD-L1 inhibitors, PD-L1 expression in HER2-positive breast cancers has not been fully determined

Methods

Results

Conclusion