TY - JOUR
T1 - Tumor-derived vaccines containing CD200 inhibit immune activation
T2 - Implications for immunotherapy
AU - Xiong, Zhengming
AU - Ampudia-Mesias, Elisabet
AU - Shaver, Rob
AU - Horbinski, Craig M.
AU - Moertel, Christopher L.
AU - Olin, Michael R.
N1 - Publisher Copyright:
© 2016 Future Medicine Ltd.
PY - 2016/9
Y1 - 2016/9
N2 - There are over 400 ongoing clinical trials using tumor-derived vaccines. This approach is especially attractive for many types of brain tumors, including glioblastoma, yet so far the clinical response is highly variable. One contributor to poor response is CD200, which acts as a checkpoint blockade, inducing immune tolerance. We demonstrate that, in response to vaccination, glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune tolerance. The addition of the CD200 inhibitor significantly increased leukocyte infiltration into the vaccine site, cytokine and chemokine production, and cytolytic activity. Our data therefore suggest that CD200 suppresses the immune system's response to vaccines, and that blocking CD200 could improve the efficacy of cancer immunotherapy.
AB - There are over 400 ongoing clinical trials using tumor-derived vaccines. This approach is especially attractive for many types of brain tumors, including glioblastoma, yet so far the clinical response is highly variable. One contributor to poor response is CD200, which acts as a checkpoint blockade, inducing immune tolerance. We demonstrate that, in response to vaccination, glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune tolerance. The addition of the CD200 inhibitor significantly increased leukocyte infiltration into the vaccine site, cytokine and chemokine production, and cytolytic activity. Our data therefore suggest that CD200 suppresses the immune system's response to vaccines, and that blocking CD200 could improve the efficacy of cancer immunotherapy.
KW - CD200 protein
KW - checkpoint blockade
KW - immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=84981215182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84981215182&partnerID=8YFLogxK
U2 - 10.2217/imt-2016-0033
DO - 10.2217/imt-2016-0033
M3 - Article
C2 - 27485078
AN - SCOPUS:84981215182
SN - 1750-743X
VL - 8
SP - 1059
EP - 1071
JO - Immunotherapy
JF - Immunotherapy
IS - 9
ER -