PURPOSE - Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development.
METHODS - Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients.
RESULTS - We found that CD14(+)HLA-DR(lo/neg) monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14(+)HLA-DR(lo/neg) monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2.
CONCLUSIONS - Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome. Clin Cancer Res; 1-10. ©2015 AACR.
Clin Cancer Res. 2015 May 21. [Epub ahead of print]
Gustafson MP1, Lin Y2, Bleeker JS3, Warad D4, Tollefson MK5, Crispen PL6, Bulur PA1, Harrington SM7, Laborde RR1, Gastineau DA8, Leibovich BC5, Cheville JC9, Kwon ED5, Dietz AB10.
1 Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
2 Division of Hematology, Mayo Clinic, Rochester, Minnesota.
3 Division of Hematology, Sanford Health, Sioux Falls, South Dakota.
4 Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, Minnesota.
5 Department of Urology, Mayo Clinic, Rochester, Minnesota.
6 Department of Urology, University of Florida, Gainesville, Florida.
7 Department of Immunology, Mayo Clinic, Rochester, Minnesota.
8 Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Division of Hematology, Mayo Clinic, Rochester, Minnesota.
9 Department of Pathology, Mayo Clinic, Rochester, Minnesota.
10 Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota