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, Samuel T Hwang

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1119-1131
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume56
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

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Keywords

  • CD4
  • Regulatory T cells
  • Tumorigenesis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Kakinuma, T., Nadiminti, H., Lonsdorf, A. S., Murakami, T., Perez, B. A., Kobayashi, H., Finkelstein, S. E., Pothiawala, G., Belkaid, Y., & Hwang, S. T. (2007). Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location. Cancer Immunology, Immunotherapy, 56(7), 1119-1131. https://doi.org/10.1007/s00262-006-0253-4