Inefficient presentation of tumor-derived antigen by tumor-infiltrating dendritic cells
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Transplantable B16 melanoma is widely used as a tumor model to investigate tumor immunity. We wished to characterize the leukocyte populations infiltrating B16 melanoma tumors, and the functional properties of tumor-infiltrating dendritic cells (TIDC).
Materials and methods
We used the B16 melanoma cell line expressing ovalbumin protein (OVA) to investigate the phenotype and T cell stimulatory capacity of TIDC.
The majority of leukocytes in B16 melanoma were macrophages, which colocalized with TIDCs, B and T cells to the peripheral area of the tumor. Both myeloid and plasmacytoid DC populations were present within tumors. Most of these DCs appeared immature, but about a third expressed a mature phenotype. TIDCs did not present tumor-derived antigen, as they were unable to induce the proliferation of tumor-specific CD4+ and CD8+ T cells in vitro unless in the presence of specific peptides. Some presentation of tumor-derived antigen could be demonstrated in the tumor-draining lymph node using in vivo proliferation assays. However, while proliferation of CD8+ T cells was reproducibly demonstrated, no proliferation of CD4+ T cells was observed.
In summary, our data suggest that DCs in tumors have limited antigen-presenting function. Inefficient antigen presentation extends to the tumor-draining lymph node, and may affect the generation of antitumor immune responses.
KeywordsMelanoma Dendritic cells Tumor immunity
T cell receptor
Counts per minute
Carboxy-fluorescein diacetate succinimidyl ester
Peridinin chlorophyll A protein
Granulocyte/macrophages colony-stimulating factor
We thank Drs E. Lord, J.G. Frelinger and F. Carbone for generously providing cell lines and mouse strains used in this study, the staff of the Malaghan Experimental Research Facility for animal husbandry and care, and the staff of the Malaghan Institute for useful suggestions and discussion. This work was supported by research grants from the Health Research Council and Cancer Society of NZ, the Wellington Medical Research Foundation, and the Genesis Oncology Trust. PS was supported by the Erwin Schroedinger Auslandsstipendium from the Austrian Science Fund (FWF-J2479).
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