Induction of regulatory T cells (Treg) is an important mechanism leading to tolerance against tumors.
Increased levels of Treg have been described in renal cell carcinoma (RCC) patients and seem to correlate with an adverse outcome. Our study aimed to analyze the influence of sorafenib and sunitinib on the frequency of Treg in patients with metastatic RCC (mRCC). Treg were analyzed by flow cytometry in the peripheral blood (PB) of patients (n=19) with histologically confirmed mRCC under treatment with either sunitinib (50 mg/d, n=11) or sorafenib (800 mg/d, n=8). Blood samples were taken before treatment and during the first, second, and third months of therapy. Flow cytometric analysis of PB mononuclear cells was performed using fluorochrome-labeled antibodies against CD3, CD4, CD25, and FOXp3. During the first month of therapy, patients treated with sorafenib showed a significant increase in FOXp3+CD3+CD4+CD25+ Treg (13.5 vs. 36.3% of gated cells, P=0.02, or 0.35 vs. 0.49% of total cells) and the ratio FOXp3pos T cells/FOXp3neg T cells (0.16 vs. 0.56 of gated cells, P=0.02). These elevated levels persisted throughout the treatment period. There was no influence of sunitinib on the frequency of Treg in our cohort of patients. Sorafenib, but not sunitinib, leads to an early and sustained increase in Treg in PB of mRCC patients. In immunoresponsive tumors such as RCC, immunological effects of kinase inhibitors are particularly relevant for the design of combination trials with immunotherapeutic agents. Our study suggests that sorafenib should be avoided in such a therapeutic setting.
Written by:
Flörcken A, Takvorian A, Van Lessen A, Singh A, Hopfenmüller W, Dörken B, Pezzutto A, Westermann J. Are you the author?
Departments of Hematology, Oncology, and Tumorimmunology; Biometry and Clinical Epidemiology, Charité-University Medicine Berlin, Berlin, Germany.
Reference: Anticancer Drugs. 2011 Dec 12. Epub ahead of print.
doi: 10.1097/CAD.0b013e32834ee2b1
PubMed Abstract
PMID: 22156795
