1. Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location
- Author
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Takashi Kakinuma, Yasmine Belkaid, Hari Nadiminti, Samuel T Hwang, Takashi Murakami, Bradford A. Perez, Anke S. Lonsdorf, Gulnar Pothiawala, Steven E. Finkelstein, and Hisataka Kobayashi
- Subjects
CD4-Positive T-Lymphocytes ,Cancer Research ,Pathology ,medicine.medical_specialty ,Neoplasm, Residual ,Skin Neoplasms ,Immunology ,Melanoma, Experimental ,chemical and pharmacologic phenomena ,Biology ,Mice ,Interleukin 21 ,T-Lymphocyte Subsets ,Immunity ,Cell Line, Tumor ,medicine ,Animals ,Immunology and Allergy ,Neoplasm ,IL-2 receptor ,neoplasms ,integumentary system ,Reverse Transcriptase Polymerase Chain Reaction ,Melanoma ,Interleukin-2 Receptor alpha Subunit ,FOXP3 ,Forkhead Transcription Factors ,hemic and immune systems ,Flow Cytometry ,medicine.disease ,Molecular biology ,Oncology ,Cell culture ,Disease Progression ,Interleukin 12 ,Female ,Neoplasm Transplantation - 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.
- Published
- 2006