Enhanced tumor responses to dendritic cells in the absence of CD8-positive cells |
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Authors: | Ribas Antoni Wargo Jennifer A Comin-Anduix Begonya Sanetti Shelley Schumacher Lana Y McLean Colin Dissette Vivian B Glaspy John A McBride William H Butterfield Lisa H Economou James S |
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Affiliation: | Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, CA 90095, USA. aribas@mednet.ucla.edu |
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Abstract: | Wild-type mice immunized with MART-1 melanoma Ag-engineered dendritic cells (DC) generate strong Ag-specific immunity that has an absolute requirement for both CD8(+) and CD4(+) T cells. DC administration to CD8 alpha knockout mice displayed unexpectedly enhanced levels of protection to tumor challenge despite this deficiency in CD8(+) T cells and the inability to mount MHC class I-restricted immune responses. This model has the following features: 1) antitumor protection is Ag independent; 2) had an absolute requirement for CD4(+) and NK1.1(+) cells; 3) CD4(+) splenocytes are responsible for cytokine production; 4) lytic cells in microcytotoxicity assays express NK, but lack T cell markers (NK1.1(+) alpha beta TCR(-) CD3(-)); and 5) the lytic phenotype can be transferred to naive CD8 alpha knockout mice by NK1.1(+) splenocytes. Elucidation of the signaling events that activate these effective cytotoxic cells and the putative suppressive mechanisms in a wild-type environment may provide means to enhance the clinical activity of DC-based approaches. |
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