Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location.
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.
Kakinuma
Takashi
T
Dermatology Branch, Center for Cancer Research, NCI, Bldg 10/Rm12N246, 10 Center Dr., Bethesda, MD 20892-1908, USA.
Nadiminti
Hari
H
Lonsdorf
Anke S
AS
Murakami
Takashi
T
Perez
Bradford A
BA
Kobayashi
Hisataka
H
Finkelstein
Steven E
SE
Pothiawala
Gulnar
G
Belkaid
Yasmine
Y
Hwang
Sam T
ST
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit