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

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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
StatePublished - Dec 15 2003
Externally publishedYes

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Chemokine CCL19
Human Herpesvirus 4
Lung Neoplasms
Ligands
Neoplasms
T-Lymphocytes
Dendritic Cells
T-Lymphocyte Subsets
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Immunosuppressive Agents
Tumor Burden
Dinoprostone
Immunotherapy
Immunity
Injections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hillinger, S., Yang, S. C., Zhu, L., Huang, M., Duckett, R., Atianzar, K. C., ... 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.

EBV-Induced Molecule 1 Ligand Chemokine (ELC/CCL19) Promotes IFN-γ-Dependent Antitumor Responses in a Lung Cancer Model. / Hillinger, Sven; Yang, Seok Chul; Zhu, Li; Huang, Min; Duckett, Russell; Atianzar, Kimberly Calica; Batra, Raj K.; Strieter, Robert M.; Dubinett, Steven M.; Sharma, Sherven.

In: Journal of Immunology, Vol. 171, No. 12, 15.12.2003, p. 6457-6465.

Research output: Contribution to journalArticle

Hillinger, S, Yang, SC, Zhu, L, Huang, M, Duckett, R, Atianzar, KC, Batra, RK, Strieter, RM, Dubinett, SM & 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, vol. 171, no. 12, pp. 6457-6465.
Hillinger, Sven ; Yang, Seok Chul ; Zhu, Li ; Huang, Min ; Duckett, Russell ; Atianzar, Kimberly Calica ; Batra, Raj K. ; Strieter, Robert M. ; Dubinett, Steven M. ; Sharma, Sherven. / EBV-Induced Molecule 1 Ligand Chemokine (ELC/CCL19) Promotes IFN-γ-Dependent Antitumor Responses in a Lung Cancer Model. In: Journal of Immunology. 2003 ; Vol. 171, No. 12. pp. 6457-6465.
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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.",
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