Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c+ dendritic cell frequency predicts progression-free survival

Hester van Cruijsen, Astrid A M van der Veldt, Laura Vroling, Dinja Oosterhoff, Henk J Broxterman, Rik J Scheper, Giuseppe Giaccone, John B A G Haanen, Alfons J M van den Eertwegh, Epie Boven, Klaas Hoekman, Tanja D de Gruijl

Research output: Contribution to journalArticleAcademicpeer-review

124 Citations (Scopus)

Abstract

PURPOSE: A disturbed myeloid lineage development with abnormally abundant neutrophils and impaired dendritic cell (DC) differentiation may contribute to tumor immune escape. We investigated the effect of sunitinib, a tyrosine kinase inhibitor of fms-like tyrosine kinase-3, KIT, and vascular endothelial growth factor receptors, on myeloid differentiation in renal cell cancer (RCC) patients.

EXPERIMENTAL DESIGN: Twenty-six advanced RCC patients were treated with sunitinib in a 4-week on/2-week off schedule. Enumeration and extensive phenotyping of myeloid subsets in the blood was done at baseline and at weeks 4 and 6 of the first treatment cycle. Baseline patient data were compared with sex- and age-matched healthy donor data.

RESULTS: Baseline frequencies of DC subsets were lower in RCC patients than in healthy donors. After 4 weeks of sunitinib treatment, a generalized decrease in myeloid frequencies was observed. Whereas neutrophils and monocytes, which were both abnormally high at baseline, remained low during the 2-week off period, DC rates recovered, resulting in a normalized myeloid lineage distribution. Subsequent to sunitinib treatment, an increase to high levels of myeloid DC (MDC) subset frequencies relative to other myeloid subsets, was specifically observed in patients experiencing tumor regression. Moreover, high CD1c/BDCA-1(+) MDC frequencies were predictive for tumor regression and improved progression-free survival.

CONCLUSION: The sunitinib-induced myeloid lineage redistribution observed in advanced RCC patients is consistent with an improved immune status. Immunologic recovery may contribute to clinical efficacy as suggested by the finding of highly increased MDC frequencies relative to other myeloid subsets in patients with tumor regression.

Original languageEnglish
Pages (from-to)5884-92
Number of pages9
JournalClinical Cancer Research : an official journal of the American Association for Cancer Research
Volume14
Issue number18
DOIs
Publication statusPublished - 15 Sept 2008
Externally publishedYes

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