Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: Implications for live kidney cancer vaccines

The clinical impact of dendritic cells (DCs) in the treatment of human canc er depends on their unique role as the most potent antigen-presenting cells that are capable of priming an antitumor T-cell response. Here, we demonst rate that functional DCs can be generated from peripheral blood of patients with metastatic renal cell carcinoma (RCC) by culture of monocytes/macroph ages (CD14(+)) in autologous serum containing medium (RPMI) in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL) 4 , For testing the capability of RCC-antigen uptake and processing, we loade d these DCs with autologous tumor lysate (TuLy) using liposomes, after whic h cytometric analysis of the DCs revealed a markedly increased expression o f HLA class I antigen and a persistent high expression of class II. The imm unogenicity of DC-TuLy was further tested in cultures of renal tumor infilt rating lymphocytes (TILs) cultured in low-dose IL-2 (20 Biologic Response M odifier Program units/ml). A synergistic effect of DC-TuLy and IL-2 in stim ulating a T cell-dependent immune response was demonstrated by: (a) the inc rease of growth expansion of TILs (9.4-14.3-fold; day 21); (b) the up-regul ation of the CD3(+)CD56(-)TcR(+) (both CD4(+) and CD8(+)) cell population; (c) the augmentation of T cell-restricted autologous tumor lysis; and (d) t he enhancement of IFN-gamma, tumor necrosis factor-alpha, granulocyte macro phage colony-stimulating factor, and IL-6 mRNA expression by TILs. Taken to gether, these data implicate that DC-TuLy can activate immunosuppressed TIL via an induction of enhanced antitumor CTL responses associated with produ ction of Th1 cells. This indicates a potential role of DC-TuLy vaccines for induction of active immunity in patients with advanced RCC.