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Publication : Interferon γ limits the effectiveness of melanoma peptide vaccines.

First Author  Cho HI Year  2011
Journal  Blood Volume  117
Issue  1 Pages  135-44
PubMed ID  20889921 Mgi Jnum  J:168428
Mgi Id  MGI:4888190 Doi  10.1182/blood-2010-08-298117
Citation  Cho HI, et al. (2011) Interferon gamma limits the effectiveness of melanoma peptide vaccines. Blood 117(1):135-44
abstractText  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 gamma (IFNgamma), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNgamma 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 IFNgamma are curtailed.
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