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 language | English (US) |
|---|---|
| Pages (from-to) | 135-144 |
| Number of pages | 10 |
| Journal | Blood |
| Volume | 117 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Interferon γ limits the effectiveness of melanoma peptide vaccines
AU - Cho, Hyun Il
AU - Lee, Young Ran
AU - Celis, Esteban
PY - 2011/1/6
Y1 - 2011/1/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650983452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650983452&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-08-298117
DO - 10.1182/blood-2010-08-298117
M3 - Article
C2 - 20889921
AN - SCOPUS:78650983452
VL - 117
SP - 135
EP - 144
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -