Renal Cell Carcinoma-induced Immunosuppression: An Immunophenotypic Study of Lymphocyte Subpopulations and Circulating Dendritic Cells

Abstract

Background: Renal cell carcinoma (RCC)-induced immune dysfunction in patients at first diagnosis was investigated. Patients and Methods: The main circulating lymphocyte subsets, the total number of circulating and intratumor dendritic cells and the titers of circulating VEGF were quantified in 47 RCC patients, using flow cytometric, immunohistochemical and ELISA assays. Results: Despite a significant activation of CD3/HLA-DR⁺ lymphocytes and of the CD56⁺ NK subset, RCC patients presented a marked immunosuppression of CD4/CD45RA naïve T-cells, CD4/CD45RO memory T-cells, CD16⁺ NK-cells, and total circulating dendritic cells, as well as a significant increase of lymphocytes co-expressing the CD4 and CD8 antigens. Finally, CD16⁺/CD56⁺ NK and DCs were poorly represented in tumor specimens. Conclusion: The complex immunological dysfunctions demonstrated involve different levels of immunocompetence and indicate a pattern of major disturbance of the immune system.