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

Autor: Takashi Kakinuma, Yasmine Belkaid, Hari Nadiminti, Samuel T Hwang, Takashi Murakami, Bradford A. Perez, Anke S. Lonsdorf, Gulnar Pothiawala, Steven E. Finkelstein, Hisataka Kobayashi
Rok vydání: 2006
Předmět:
Zdroj: Cancer Immunology, Immunotherapy. 56:1119-1131
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s00262-006-0253-4
Popis: 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.
Databáze: OpenAIRE