Interferon γ limits the effectiveness of melanoma peptide vaccines.

Abstract

The development of effective therapeutic vaccines to generate tumor-reactive cytotoxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradicate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a peptide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects decreased in the presence of interferon γ (IFNγ), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNγ evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vaccines can eradicate large, established tumors in circumstances under which the inhibitory activities of IFNγ are curtailed.

• Authors: Hyun-Il Cho, Young-Ran Lee, Esteban Celis
• Journal: Blood (Blood) Vol. 117 Issue 1 Pg. 135-44 (Jan 06 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 20889921 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Cancer Vaccines
• Receptors, Antigen, T-Cell
• Vaccines, Subunit
• Interferon-gamma

Topics

• Animals
• Antiviral Agents (pharmacology)
• Cancer Vaccines (pharmacology)
• Female
• Genes, MHC Class I (physiology)
• Humans
• Immunization
• Interferon-gamma (pharmacology)
• Lymphocyte Activation
• Melanoma, Experimental (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Receptors, Antigen, T-Cell (metabolism)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured
• Vaccines, Subunit (pharmacology)