Cancer Immunology, Immunotherapy

, Volume 56, Issue 7, pp 1119–1131

Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location

  • Takashi Kakinuma
  • Hari Nadiminti
  • Anke S. Lonsdorf
  • Takashi Murakami
  • Bradford A. Perez
  • Hisataka Kobayashi
  • Steven E. Finkelstein
  • Gulnar Pothiawala
  • Yasmine Belkaid
  • Sam T. Hwang
Original Article

DOI: 10.1007/s00262-006-0253-4

Cite this article as:
Kakinuma, T., Nadiminti, H., Lonsdorf, A.S. et al. Cancer Immunol Immunother (2007) 56: 1119. doi:10.1007/s00262-006-0253-4

Abstract

Luciferase-transduced B16 murine melanoma cells (luc-B16) inoculated in ear skin do not form tumors but prevent tumor formation by luc-B16 cells injected into the footpad. To determine the requirements for such immunity, we followed the fate of luc-B16 cells following ear injection. Surprisingly, small numbers of viable luc-B16 cells were detected in tumor-free mouse skin for up to 60 days post-inoculation. After 1 week, the number of Foxp3+CD4+CD25+ T cells (along with foxp3 mRNA expression) increased rapidly in the injected ear skin. Residual tumor cells in ears were reduced in mice treated with anti-CD25 mAb and in CD4-deficient mice, but increased in CD8-deficient mice. Strikingly, the loss of luc-B16 cells in the ear skin, either spontaneously or following amputation of the injected ear, resulted in significantly enhanced tumor formation by parental and luciferase-expressing B16 cells after footpad injection. These studies suggest that small numbers of tumor cells (possibly regulated by CD4+CD25+ regulatory T cells expressing Foxp3) are required for effective host anti-tumor responses at alternate inoculation sites.

Keywords

TumorigenesisRegulatory T cellsCD4

Abbreviations

Tregs

Regulatory T cells

luc

Luciferase

CTL

Cytolytic T lymphocytes (cells)

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Takashi Kakinuma
    • 4
  • Hari Nadiminti
    • 4
  • Anke S. Lonsdorf
    • 4
  • Takashi Murakami
    • 4
  • Bradford A. Perez
    • 4
  • Hisataka Kobayashi
    • 2
  • Steven E. Finkelstein
    • 3
  • Gulnar Pothiawala
    • 1
  • Yasmine Belkaid
    • 1
  • Sam T. Hwang
    • 4
  1. 1.Laboratory of Parasitic DiseasesNIAIDBethesdaUSA
  2. 2.Metabolism BranchCenter for Cancer Research, NCIBethesdaUSA
  3. 3.Surgery BranchCenter for Cancer Research, NCIBethesdaUSA
  4. 4.Dermatology BranchCenter for Cancer Research, NCIBethesdaUSA