Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer. Issue 1 (6th February 2019)

• Record Type: Journal Article
• Authors: Yeong, Joe; Lim, Jeffrey Chun Tatt; Lee, Bernett; Li, Huihua; Ong, Clara Chong Hui; Thike, Aye Aye; Yeap, Wei Hseun; Yang, Yi; Lim, Ansel Yi Herh; Tay, Timothy Kwang Yong; Liu, Jin; Wong, Siew-Cheng; Chen, Jinmiao; Lim, Elaine Hsuen; Iqbal, Jabed; Dent, Rebecca; Newell, Evan W.; Tan, Puay Hoon
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-02-06
• Subjects: TNBC -- PD-1 -- PD-L1 -- Immune checkpoint -- IFNG; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0499-y
• Languages: English
• ISSNs: 2051-1426

Abstract

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 CD8 − PD-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 (ΔLRχ 2 = 6.35; P = 0.041) and OS (ΔLRχ 2 = 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.