Mitotane treatment of adrenocortical carcinoma induces tumoural secretion of GDF-15: impact on poor prognosis and impaired responsiveness to immunotherapy
Authors' conclusion
Mitotane increases GDF-15 levels and is associated with poor response to ICI. GDF-15 may mediate reduced infiltration with immune cells in ACC.
Study context
- Population
- Patients with adrenocortical carcinoma (ACC); second cohort of 46 ACC patients receiving immune checkpoint inhibition (ICI) (14 responders); 58 ACC tumour samplesplus ICI cohort of 46
- Participants
- 151 patients
- Exposure
- Low vs high serum GDF-15
- Outcome
- Value of serum GDF-15 for prognosis of ACC and as predictor of response to ICI
Methodological detailsserum biomarker study, tumour mRNA expression analysis
- Serum biomarker study
- Tumour mRNA expression analysis
Main finding
As reported in the abstract
Patient survival by serum GDF-15
- Serum GDF-15 below the median associated with significantly longer patient survival
- GDF-15 induction in ACC cells and patients upon mitotane treatment
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| GDF-15 levels, ICI responders vs non-respondersSignificantly lower GDF-15 in responders | P = 0.0379 |
| PFS on ICI by GDF-15Low GDF-15 vs High GDF-15 · significantly longer PFS with low GDF-15 | P = 0.036 |
Pro-inflammatory immune-related gene expression in ACC tissue
- Lower in ACC tissue with GDF-15 expression above the median
Original publication
Mitotane treatment of adrenocortical carcinoma induces tumoural secretion of GDF-15: impact on poor prognosis and impaired responsiveness to immunotherapy. Eur J Endocrinol. Published 26 June 2025. doi:10.
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