Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model

Amer N. Kalaaji, Jun Lu, Svetomir N. Markovic, Esteban Celis, Mark R. Pittelkow

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Various cytokines, including interferon α (IFNα), tumor necrosis factor α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been used as adjuvant therapy for advanced-stage melanoma with some success but with marked toxicity, which appears to be related to higher doses. We investigated the efficacy of IFNα, GM-CSF, and TNFα in various combinations to induce antitumor and immune responses in a B16F10 murine melanoma model. These studies showed that GM-CSF, IFNα, and TNFα, when injected together intratumorally, mediated significant inhibition of tumor growth. Tumor regression correlated with local tumor necrosis and significant infiltration of T cells. In addition, this injected intralesional cytokine cocktail also induced lymphadenopathy, with an increase in both CD4+ and CD8+ T cells in the draining lymph nodes. Furthermore, tumor-specific CD8+ T cells were identified from draining lymph nodes. These investigations identify the combined effects of IFNα, GM-CSF, and TNFα in induction of the adaptive immune response and generation of antigen-specific T-cell reactivity. These results support potential clinical trials of the low-dose cytokine combination as adjuvant therapy for melanoma.

Original languageEnglish (US)
Pages (from-to)287-293
Number of pages7
JournalCytokine
Volume49
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

T-cells
Granulocyte-Macrophage Colony-Stimulating Factor
Interferons
Tumors
Melanoma
Tumor Necrosis Factor-alpha
Cytokines
T-Lymphocytes
Growth
Neoplasms
Lymph Nodes
Histocompatibility Antigens Class II
Adaptive Immunity
Therapeutics
Infiltration
Toxicity
Necrosis
Clinical Trials
Antigens

Keywords

  • Cytokines
  • Cytotoxic T lymphocytes
  • Melanoma
  • Therapy
  • Tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model. / Kalaaji, Amer N.; Lu, Jun; Markovic, Svetomir N.; Celis, Esteban; Pittelkow, Mark R.

In: Cytokine, Vol. 49, No. 3, 01.03.2010, p. 287-293.

Research output: Contribution to journalArticle

Kalaaji, Amer N. ; Lu, Jun ; Markovic, Svetomir N. ; Celis, Esteban ; Pittelkow, Mark R. / Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model. In: Cytokine. 2010 ; Vol. 49, No. 3. pp. 287-293.
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