Interferon γ limits the effectiveness of melanoma peptide vaccines

Hyun Il Cho, Young Ran Lee, Esteban Celis

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalBlood
Volume117
Issue number1
DOIs
StatePublished - Jan 6 2011

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Subunit Vaccines
T-cells
Interferons
Tumors
Melanoma
Cytotoxic T-Lymphocytes
Neoplasms
Vaccines
Bearings (structural)
Immunosuppressive Agents
Major Histocompatibility Complex
Chemical activation
Cytokines
T-Lymphocytes
Molecules
Therapeutics
Research

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Interferon γ limits the effectiveness of melanoma peptide vaccines. / Cho, Hyun Il; Lee, Young Ran; Celis, Esteban.

In: Blood, Vol. 117, No. 1, 06.01.2011, p. 135-144.

Research output: Contribution to journalArticle

Cho, Hyun Il ; Lee, Young Ran ; Celis, Esteban. / Interferon γ limits the effectiveness of melanoma peptide vaccines. In: Blood. 2011 ; Vol. 117, No. 1. pp. 135-144.
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