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Updated: Jul 22, 2025

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Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment

Markus Haake1,2, Beatrice Haack1, Tina Schäfer1

  • 1Department of Gynecology, University Hospital Würzburg, Würzburg, Germany.

Nature Communications
|July 20, 2023
PubMed

Insights

Growth differentiation factor 15 (GDF-15) hinders T cell infiltration into tumors, impacting immunotherapy response. Neutralizing GDF-15 enhances T cell trafficking and improves cancer treatment efficacy.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Immune checkpoint blockade therapy offers curative potential for some cancers but lacks efficacy in the majority of patients.
  • Pre-existing T cell infiltrates are known predictors of response to checkpoint-based immunotherapy across various tumor types.

Purpose of the Study:

  • To investigate the role of Growth Differentiation Factor 15 (GDF-15) in regulating T cell extravasation into the tumor microenvironment.
  • To determine the correlation between GDF-15 levels and response to PD-1-based immune checkpoint blockade therapy in melanoma patients.

Main Methods:

  • In vitro pharmacological studies using T cells and endothelial cells.
  • In vivo experiments utilizing murine tumor models.
  • Analysis of serum GDF-15 levels in human melanoma patients undergoing immunotherapy.

Main Results:

  • GDF-15 was shown to impair T cell adhesion to activated endothelial cells, a critical step for T cell extravasation.
  • Elevated serum GDF-15 levels in melanoma patients strongly correlated with treatment failure in PD-1-based immunotherapy.
  • Neutralization of GDF-15 in murine models enhanced T cell trafficking and improved therapeutic outcomes.

Conclusions:

  • GDF-15 acts as a novel regulator of T cell extravasation into tumors, independent of its known roles in cancer cachexia.
  • GDF-15 represents a potential predictive biomarker for immunotherapy response.
  • Therapeutic strategies targeting GDF-15, such as anti-GDF-15 antibodies, warrant further investigation to improve cancer immunotherapy efficacy.

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