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

Abstract

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.

• Authors: Sven Hillinger, Seok-Chul Yang, Li Zhu, Min Huang, Russell Duckett, Kimberly Atianzar, Raj K Batra, Robert M Strieter, Steven M Dubinett, Sherven Sharma
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 171 Issue 12 Pg. 6457-65 (Dec 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 14662845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• CCL19 protein, human
• Ccl19 protein, mouse
• Ccl9 protein, mouse
• Chemokine CCL19
• Chemokine CXCL10
• Chemokines
• Chemokines, CC
• Chemokines, CXC
• Cytokines
• Macrophage Inflammatory Proteins
• Transforming Growth Factor beta
• Interferon-gamma
• Dinoprostone

Topics

• Adoptive Transfer
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Cell Line, Tumor
• Cell Movement (immunology)
• Chemokine CCL19
• Chemokine CXCL10
• Chemokines (metabolism)
• Chemokines, CC (administration & dosage, physiology)
• Chemokines, CXC (physiology)
• Cytokines (metabolism)
• Dendritic Cells (cytology, immunology)
• Dinoprostone (antagonists & inhibitors, biosynthesis)
• Female
• Herpesvirus 4, Human (immunology)
• Injections, Intralesional
• Interferon-gamma (biosynthesis, physiology)
• Leukocyte Count
• Lung Neoplasms (immunology, metabolism, pathology, therapy)
• Lymphocyte Count
• Macrophage Inflammatory Proteins (physiology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• T-Lymphocyte Subsets (cytology, immunology, transplantation)
• Th1 Cells (immunology, metabolism)
• Transforming Growth Factor beta (antagonists & inhibitors, biosynthesis)