EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent antitumor responses in a lung cancer model.
The antitumor efficacy of EBV-induced molecule 1 ligand CC chemokine (ELC/CCL19) was evaluated in a murine lung cancer model. The ability of ELC/CCL19 to chemoattract both dendritic cells and T lymphocytes formed the rationale for this study. Compared with diluent-treated tumor-bearing mice, intratumoral injection of recombinant ELC/CCL19 led to significant systemic reduction in tumor volumes (p < 0.01). ELC/CCL19-treated mice exhibited an increased influx of CD4 and CD8 T cell subsets as well as dendritic cells at the tumor sites. These cell infiltrates were accompanied by increases in IFN-gamma, MIG/CXCL9, IP-10/CXCL10, GM-CSF, and IL-12 but a concomitant decrease in the immunosuppressive molecules PGE(2) and TGFbeta. Transfer of T lymphocytes from ELC/CCL19 treated tumor-bearing mice conferred the antitumor therapeutic efficacy of ELC/CCL19 to naive mice. ELC/CCL19 treated tumor-bearing mice showed enhanced frequency of tumor specific T lymphocytes secreting IFN-gamma. In vivo depletion of IFN-gamma, MIG/CXCL9, or IP-10/CXCL10 significantly reduced the antitumor efficacy of ELC/CCL19. These findings provide a strong rationale for further evaluation of ELC/CCL19 in tumor immunity and its use in cancer immunotherapy.
Hillinger
Sven
S
Department of Medicine, University of California, Los Angeles Lung Cancer Research Program, 90095-1690, USA.
Yang
Seok-Chul
SC
Zhu
Li
L
Huang
Min
M
Duckett
Russell
R
Atianzar
Kimberly
K
Batra
Raj K
RK
Strieter
Robert M
RM
Dubinett
Steven M
SM
Sharma
Sherven
S
D019264:Adoptive Transfer; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D054415:Chemokine CCL19; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000008:administration & dosage / Q000502:physiology*; D019743:Chemokines, CXC / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018655:Lymphocyte Count; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000970:Antineoplastic Agents; C515460:CCL19 protein, human; C515461:Ccl19 protein, mouse; C095218:Ccl9 protein, mouse; D054415:Chemokine CCL19; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D015232:Dinoprostone