MINIMAL RECRUITMENT AND ACTIVATION OF DENDRITIC CELLS WITHIN RENAL-CELL CARCINOMA

Dendritic cells (DCs) are predicted to participate in natural tumor im munity by migrating into tumors, where they acquire antigen, undergo a ctivation, and migrate to lymph nodes to initiate a T-lymphocyte respo nse against tumor-associated antigens, The presence of DCs using defin ed lineage markers and their function in human tumors has not been ass essed previously, The monoclonal antibodies against CMRF-44 and CD83, which are differentiation/activation antigens on DCs, were used in imm unohistological and flow cytometry studies to analyze the DC subtypes infiltrating 14 cases of human renal cell carcinoma (RCC), The functio nal immunocompetence of the DCs isolated from RCC was assessed by test ing their ability to stimulate an allogeneic mixed leukocyte reaction, The majority of leukocytes present within the RCC were macrophages (6 2% +/- 14.7) or T lymphocytes (19% +/- 9.5), with CD45(+) HLA-DR+ line age-negative putative DCs accounting for less than 10% of the leukocyt es present, Of these, a subset, comprising less than 1% of total leuko cytes, had an activated CMRF-44(+) or CD83(+) DC phenotype, Activated CMRF-44(+) and CD83(+) DCs were more evident outside the tumor in asso ciation with T-lymphocyte clusters, The number of CMRF-44(+) DCs corre lated closely with the number of S-100-positive DCs, Isolation of DCs from eight RCCs was achieved, and flow cytometry studies confirmed the small proportion of activated CMRF-44(+) DCs, The CMRF-44(+) DCs stim ulated an allogeneic mixed leukocyte reaction, but the CMRF-44(-) DCs (normal tissue DC precursors and other cells) failed to do so, These r esults suggest that RCCs recruit few DCs into the tumor substance, and the tumor environment fails to initiate the expected protective activ ation of DCs, These two mechanisms, amongst others, may contribute to tumor escape from immunosurveillance. In vitro loading of DCs with tum or-associated antigens may be a useful therapeutic maneuver.