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PD-L1 Expression in Triple-Negative Breast Cancer

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TLDR
Using tissue microarrays containing 105 triple-negative breast cancer specimens, Mittendorf and colleagues show that 20% of the TNBC specimens express PD-L1, half have lost PTEN, and inhibitors of PI3K pathway decrease PD- l1 expression, providing a rationale for therapeutic targeting of PD- L1 for TNBC.
Abstract
Early-phase trials targeting the T-cell inhibitory molecule programmed cell death ligand 1 (PD-L1) have shown clinical efficacy in cancer. This study was undertaken to determine whether PD-L1 is overexpressed in triple-negative breast cancer (TNBC) and to investigate the loss of PTEN as a mechanism of PD-L1 regulation. The Cancer Genome Atlas (TCGA) RNA sequencing data showed significantly greater expression of the PD-L1 gene in TNBC ( n = 120) compared with non-TNBC ( n = 716; P + tumors had greater CD8 + T-cell infiltrate than PD-L1 − tumors (688 cells/mm vs. 263 cells/mm; P Cancer Immunol Res; 2(4); 361–70. ©2014 AACR .

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Journal ArticleDOI

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

TL;DR: This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.
Journal ArticleDOI

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer

TL;DR: Atezolizumab plus nab‐paclitaxel prolonged progression‐free survival among patients with metastatic triple‐negative breast cancer in both the intention‐to‐treat population and the PD‐L1–positive subgroup.
Journal ArticleDOI

Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease

TL;DR: The most relevant molecular findings in TNBC from the past decade are discussed and the most promising therapeutic opportunities derived from these data are discussed.
Journal ArticleDOI

PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations

TL;DR: Evaluating several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota and the mechanisms of action of these markers clarify.
Journal ArticleDOI

Regulation and Function of the PD-L1 Checkpoint

TL;DR: The roles of the PD-1-PD-L1 axis in cancer is reviewed, focusing on recent findings on the mechanisms that regulate PD-L 1 expression at the transcriptional, posttranscriptional, and protein level, to inform the design of more precise and effective cancer immune checkpoint therapies.
References
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Journal ArticleDOI

Hallmarks of cancer: the next generation.

TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI

The blockade of immune checkpoints in cancer immunotherapy

TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI

Comprehensive molecular portraits of human breast tumours

Daniel C. Koboldt, +355 more
- 04 Oct 2012 - 
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
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