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[Cancer Research 61, 8794-8802, December 15, 2001]
© 2001 American Association for Cancer Research

Immunology

The Dynamics of the T-Cell Antitumor Response

Chemokine-secreting Dendritic Cells Can Prime Tumor-reactive T Cells Extranodally1

Christopher J. Kirk2, Dennis Hartigan-O’Connor and James J. Mulé3

Departments of Surgery [C. J. K., J. J. M.] and Internal Medicine [J. J. M.], Tumor Immunology and Immunotherapy Program of the Comprehensive Cancer Center [C. J. K., J. J. M.] and the Program in Cellular and Molecular Biology [D. H-O.], University of Michigan Medical Center, Ann Arbor, Michigan 48109-0666

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.




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Copyright © 2001 by the American Association for Cancer Research.