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.
Kirk
C J
CJ
Department of Surgery, Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor 48109-0666, USA.
Hartigan-O'Connor
D
D
Nickoloff
B J
BJ
Chamberlain
J S
JS
Giedlin
M
M
Aukerman
L
L
Mule
J J
JJ
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