All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients

Abnormal dendritic cell differentiation and accumulation of immature myeloid suppressor cells (ImC) is one of the major mechanisms of tumor escape. We tested the possibility of pharmacologic regulation of myeloid cell differentiation using all-trans-retinoic acid (ATRA). Eighteen patients with metas...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-09, Vol.66 (18), p.9299-9307
Main Authors: MIRZA, Noweeda, FISHMAN, Mayer, FRICKE, Ingo, DUNN, Mary, NEUGER, Anthony M, FROST, Timothy J, LUSH, Richard M, ANTONIA, Scott, GABRILOVICH, Dmitry I
Format: Article
Language:English
Subjects:
Aged
Antineoplastic agents
Biological and medical sciences
Carcinoma, Renal Cell - blood
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - immunology
Cell Differentiation - drug effects
Cell Differentiation - immunology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Female
Humans
Interleukin-2 - therapeutic use
Kidney Neoplasms - blood
Kidney Neoplasms - drug therapy
Kidney Neoplasms - immunology
Male
Medical sciences
Middle Aged
Myeloid Cells - drug effects
Myeloid Cells - immunology
Myeloid Cells - pathology
Pharmacology. Drug treatments
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Tretinoin - blood
Tretinoin - pharmacokinetics
Tretinoin - therapeutic use
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Summary:Abnormal dendritic cell differentiation and accumulation of immature myeloid suppressor cells (ImC) is one of the major mechanisms of tumor escape. We tested the possibility of pharmacologic regulation of myeloid cell differentiation using all-trans-retinoic acid (ATRA). Eighteen patients with metastatic renal cell carcinoma were treated with ATRA followed by s.c. interleukin 2 (IL-2). Eight healthy individuals comprised a control group. As expected, the cancer patients had substantially elevated levels of ImC. We observed that ATRA dramatically reduced the number of ImC. This effect was observed only in patients with high plasma concentration of ATRA (>150 ng/mL), but not in patients with lower ATRA concentrations (
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-06-1690