The dynamics of the T-cell antitumor response: chemokine-secreting dendritic cells can prime tumor-reactive T cells extranodally.
Direct administration of dendritic cells (DCs) genetically modified to express secondary lymphoid tissue chemokine (SLC) into growing B16 melanoma could result in a substantial, sustained influx of T cells within the mass with only a transient increase in T-cell numbers in the draining lymph node (DLN). DCs were retained at the tumor site with only a very small percentage trafficking to the DLN. The T cells infiltrating the tumor mass expressed the activation marker CD25 within 24 h and developed IFN-gamma-secreting function within 7 days as tumor growth was inhibited. Similar results were obtained in lymphotoxin alpha-/- mice, which lacked peripheral lymph nodes. Our data demonstrate that effective T-cell priming can occur extranodally and result in measurable antitumor effects in vivo.
Kirk
C J
CJ
Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0666, USA.
Hartigan-O'Connor
D
D
Mulé
J J
JJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D008233:Lymphotoxin-alpha; D007371:Interferon-gamma