Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Joe Yeong, Jeffrey Chun Tatt Lim, Bernett Lee, Huihua Li, Clara Chong Hui Ong, Aye Aye Thike, Wei Hseun Yeap, Yi Yang, Ansel Yi Herh Lim, Timothy Kwang Yong Tay, Jin Liu, Siew-Cheng Wong, Jinmiao Chen, Elaine Hsuen Lim, Jabed Iqbal, Rebecca Dent, Evan W. Newell, Puay Hoon Tan

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 (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. More... »

PAGES

34

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s40425-019-0499-y

    DOI

    http://dx.doi.org/10.1186/s40425-019-0499-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111954631

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30728081


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