TY - JOUR
T1 - Intratumoral CD14+ cells and circulating CD14+HLA-DRlo/neg monocytes correlate with decreased survival in patients with clear cell renal cell carcinoma
AU - Gustafson, Michael P.
AU - Lin, Yi
AU - Bleeker, Jonathan S.
AU - Warad, Deepti
AU - Tollefson, Matthew K.
AU - Crispen, Paul L.
AU - Bulur, Peggy A.
AU - Harrington, Susan M.
AU - Laborde, Rebecca R.
AU - Gastineau, Dennis A.
AU - Leibovich, Bradley C.
AU - Cheville, John C.
AU - Kwon, Eugene D.
AU - Dietz, Allan B.
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/9/15
Y1 - 2015/9/15
N2 - 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. Experimental Design: 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-DRlo/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-DRlo/neg monocytes was found to correlate with the intensity ofCD14 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 ofmutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome. Clin Cancer Res; 21(18); 4224-33.
AB - 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. Experimental Design: 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-DRlo/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-DRlo/neg monocytes was found to correlate with the intensity ofCD14 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 ofmutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome. Clin Cancer Res; 21(18); 4224-33.
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U2 - 10.1158/1078-0432.CCR-15-0260
DO - 10.1158/1078-0432.CCR-15-0260
M3 - Article
C2 - 25999436
AN - SCOPUS:84942909842
SN - 1078-0432
VL - 21
SP - 4224
EP - 4233
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -