[HTML][HTML] Prognostic value of CD8+ PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer

J Yeong, JCT Lim, B Lee, H Li, CCH Ong… - … for immunotherapy of …, 2019 - Springer
J Yeong, JCT Lim, B Lee, H Li, CCH Ong, AA Thike, WH Yeap, Y Yang, AYH Lim, TKY Tay
Journal for immunotherapy of cancer, 2019Springer
The role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1)
in triple negative breast cancer (TNBC) remains to be fully understood. In this study, we
investigated the role of PD-1 as a prognostic marker for TNBC in an Asian cohort (n= 269).
Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1,
and subjected to NanoString assays to measure the expression of immune-related genes.
Associations between disease-free survival (DFS), overall survival (OS) and biomarker …
Abstract
The role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) in triple negative breast cancer (TNBC) remains to be fully understood. In this study, we investigated the role of PD-1 as a prognostic marker for TNBC in an Asian cohort (n = 269). Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1, and subjected to NanoString assays to measure the expression of immune-related genes. Associations between disease-free survival (DFS), overall survival (OS) and biomarker expression were investigated. Multivariate analysis showed that tumors with high PD-1+ immune infiltrates harbored significantly increased DFS, and this increase was significant even after controlling for clinicopathological parameters (HR 0.95; P = 0.030). In addition, the density of cells expressing both CD8 and PD-1, but not the density of CD8PD-1+ immune infiltrates, was associated with improved DFS. Notably, this prognostic significance was independent of clinicopathological parameters and the densities of total CD8+ cell (HR 0.43, P = 0.011). At the transcriptional level, high expression of PDCD1 within the tumor was significantly associated with improved DFS (HR 0.38; P = 0.027). In line with these findings, high expression of IFNG (HR 0.38; P = 0.001) and IFN signaling genes (HR 0.46; p = 0.027) was also associated with favorable DFS. Inclusion of PD-1 immune infiltrates and PDCD1 gene expression added significant prognostic value for DFS (ΔLRχ2 = 6.35; P = 0.041) and OS (ΔLRχ2 = 9.53; P = 0.008), beyond that provided by classical clinicopathological variables. Thus, PD-1 mRNA and protein expression status represent a promising, independent indicator of prognosis in TNBC.
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