EBV-Induced Molecule 1 Ligand Chemokine (ELC/CCL19) Promotes IFN-γ-Dependent Antitumor Responses in a Lung Cancer Model

Sven Hillinger, Seok Chul Yang, Li Zhu, Min Huang, Russell Duckett, Kimberly Calica Atianzar, Raj K. Batra, Robert M. Strieter, Steven M. Dubinett, Sherven Sharma

Research output: Contribution to journalArticle

51 Scopus citations

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-γ, MIG/CXCL9, IP-10/CXCL10, GM-CSF, and IL-12 but a concomitant decrease in the immunosuppressive molecules PGE2 and TGFβ. 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-γ. In vivo depletion of IFN-γ, 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.

Original languageEnglish (US)
Pages (from-to)6457-6465
Number of pages9
JournalJournal of Immunology
Volume171
Issue number12
DOIs
StatePublished - Dec 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hillinger, S., Yang, S. C., Zhu, L., Huang, M., Duckett, R., Atianzar, K. C., Batra, R. K., Strieter, R. M., Dubinett, S. M., & Sharma, S. (2003). EBV-Induced Molecule 1 Ligand Chemokine (ELC/CCL19) Promotes IFN-γ-Dependent Antitumor Responses in a Lung Cancer Model. Journal of Immunology, 171(12), 6457-6465. https://doi.org/10.4049/jimmunol.171.12.6457