EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent antitumor responses in a lung cancer model

• Published in: The Journal of immunology (1950) 2003-12, Vol.171 (12), p.6457-6465
• Main Authors: Hillinger, Sven, Yang, Seok-Chul, Zhu, Li, Huang, Min, Duckett, Russell, Atianzar, Kimberly, Batra, Raj K, Strieter, Robert M, Dubinett, Steven M, Sharma, Sherven
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Movement - immunology; Chemokine CCL19; Chemokine CXCL10; Chemokines - metabolism; Chemokines, CC - administration & dosage; Chemokines, CC - physiology; Chemokines, CXC - physiology; Cytokines - metabolism; Dendritic Cells - cytology; Dendritic Cells - immunology; Dinoprostone - antagonists & inhibitors; Dinoprostone - biosynthesis; Female; Herpesvirus 4, Human - immunology; Injections, Intralesional; Interferon-gamma - biosynthesis; Interferon-gamma - physiology; Leukocyte Count; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lymphocyte Count; Macrophage Inflammatory Proteins - physiology; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - transplantation; Th1 Cells - immunology; Th1 Cells - metabolism; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.12.6457

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.