TY - JOUR
T1 - Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model
AU - Kalaaji, Amer N.
AU - Lu, Jun
AU - Markovic, Svetomir N.
AU - Celis, Esteban
AU - Pittelkow, Mark R.
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - Cytokines
KW - Cytotoxic T lymphocytes
KW - Melanoma
KW - Therapy
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=75449110531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75449110531&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2009.11.016
DO - 10.1016/j.cyto.2009.11.016
M3 - Article
C2 - 20060741
AN - SCOPUS:75449110531
SN - 1043-4666
VL - 49
SP - 287
EP - 293
JO - Cytokine
JF - Cytokine
IS - 3
ER -