T cell-dependent antitumor immunity mediated by secondary lymphoid tissue chemokine: augmentation of dendritic cell-based immunotherapy.
Secondary lymphoid tissue chemokine (SLC) is a CC chemokine that is selective in its recruitment of naive T cells and dendritic cells (DCs). In the lymph node, SLC is believed to play an important role in the initiation of an immune response by colocalizing naive T cells with DC-presenting antigen. Here, we used SLC as a treatment for tumors established from the poorly immunogenic B16 melanoma. Intratumoral injections of SLC inhibited tumor growth in a CD8+, T cell-dependent manner. SLC elicited a substantial infiltration of DCs and T cells into the tumor, coincident with the antitumor response. We next used SLC gene-modified DCs as a treatment of established tumors. Intratumoral injections of SLC-expressing DCs resulted in tumor growth inhibition that was significantly better than either control DCs or SLC alone. Distal site immunization of tumor-bearing mice with SLC gene-modified DCs pulsed with tumor lysate elicited an antitumor response whereas control DCs did not. We also found that s.c. injection of lysate-pulsed DCs expressing SLC promoted the migration of T cells to the immunization site. This report demonstrates that SLC can both induce antitumor responses and enhance the antitumor immunity elicited by DCs.
Department of Surgery, Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor 48109-0666, USA.
C J
CJ
Kirk
D
D
Hartigan-O'Connor
B J
BJ
Nickoloff
J S
JS
Chamberlain
M
M
Giedlin
L
L
Aukerman
J J
JJ
Mule
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054421:Chemokine CCL21; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D005260:Female; D015316:Genetic Therapy; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D016219:Immunotherapy, Adoptive; D015552:Injections, Intralesional; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC