Refine
Has Fulltext
- yes (4)
Is part of the Bibliography
- yes (4)
Document Type
- Journal article (4)
Language
- English (4)
Keywords
- B7-H1 (1)
- CD39 (1)
- CD73 (1)
- PC-1 blockade (1)
- PD-1 (1)
- PD-L1 (1)
- T cells (1)
- adenosine (1)
- brain metastases (1)
- breast cancer (1)
Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.