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Cancer Immunology, Immunotherapy

, Volume 57, Issue 11, pp 1665–1673 | Cite as

Inefficient presentation of tumor-derived antigen by tumor-infiltrating dendritic cells

  • Patrizia StoitznerEmail author
  • Laura K. Green
  • Jae Y. Jung
  • Kylie M. Price
  • Haley Atarea
  • Bronwyn Kivell
  • Franca Ronchese
Original Article

Abstract

Background

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.

Results

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.

Conclusion

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.

Keywords

Melanoma Dendritic cells Tumor immunity 

Abbreviations

DCs

Dendritic cells

TIDC

Tumor-infiltrating DC

LCs

Langerhans cells

OVA

Ovalbumin

TCR

T cell receptor

mAb

Monoclonal antibody

APC

Allophycocyanin

FITC

fluorescein isothiocyanate

PE

Phycoerythrin

PBS

Phosphate-buffered saline

s.c.

Subcutaneously

cpm

Counts per minute

CFSE

Carboxy-fluorescein diacetate succinimidyl ester

i.v.

Intraveneously

PerCP

Peridinin chlorophyll A protein

GM-CSF

Granulocyte/macrophages colony-stimulating factor

LPS

Lipopolysacharide

Notes

Acknowledgments

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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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Patrizia Stoitzner
    • 1
    • 2
    Email author
  • Laura K. Green
    • 1
  • Jae Y. Jung
    • 1
  • Kylie M. Price
    • 1
  • Haley Atarea
    • 1
  • Bronwyn Kivell
    • 3
  • Franca Ronchese
    • 1
  1. 1.Malaghan Institute of Medical ResearchWellingtonNew Zealand
  2. 2.Department of Dermatology and VenereologyInnsbruck Medical UniversityInnsbruckAustria
  3. 3.Victoria UniversityWellingtonNew Zealand

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