TY - JOUR
T1 - In vivo colocalization of antigen and CpG within dendritic cells is associated with the efficacy of cancer immunotherapy
AU - Nierkens, Stefan
AU - Den Brok, Martijn H.
AU - Sutmuller, Roger P.M.
AU - Grauer, Oliver M.
AU - Bennink, Erik
AU - Morgan, Mary E.
AU - Figdor, Carl G.
AU - Ruers, Theo J.M.
AU - Adema, Gosse J.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Immunostimulatory cytidyl guanosyl (CpG) motifs are of great interest as cancer vaccine adjuvants. They act as potent inducers of Th1 responses, including the activation of cytotoxic CD8+ T lymphocytes (CTL). Whereas animal models have provided clear evidence that CpG enhances antitumor immunity, clinical trials in humans have thus far been less successful. Applying cryosurgery as an instant in situ tumor destruction technique, we now show that timing of CpG administration crucially affects colocalization of antigen and CpG within EEA-1+ and LAMP-1+ compartments within dendritic cells in vivo. Moreover, antigen/CpG colocalization is directly correlated with antigen cross-presentation, the presence of CTL, and protective antitumor immunity. Thus, failure or success of CpG as a vaccine adjuvant may depend on colocalization of antigen/CpG inside DCs and hence on the timing of CpG administration. These data might aid in the design of future immunotherapeutic strategies for cancer patients.
AB - Immunostimulatory cytidyl guanosyl (CpG) motifs are of great interest as cancer vaccine adjuvants. They act as potent inducers of Th1 responses, including the activation of cytotoxic CD8+ T lymphocytes (CTL). Whereas animal models have provided clear evidence that CpG enhances antitumor immunity, clinical trials in humans have thus far been less successful. Applying cryosurgery as an instant in situ tumor destruction technique, we now show that timing of CpG administration crucially affects colocalization of antigen and CpG within EEA-1+ and LAMP-1+ compartments within dendritic cells in vivo. Moreover, antigen/CpG colocalization is directly correlated with antigen cross-presentation, the presence of CTL, and protective antitumor immunity. Thus, failure or success of CpG as a vaccine adjuvant may depend on colocalization of antigen/CpG inside DCs and hence on the timing of CpG administration. These data might aid in the design of future immunotherapeutic strategies for cancer patients.
UR - http://www.scopus.com/inward/record.url?scp=48549105859&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-6023
DO - 10.1158/0008-5472.CAN-07-6023
M3 - Article
C2 - 18593941
AN - SCOPUS:48549105859
SN - 0008-5472
VL - 68
SP - 5390
EP - 5396
JO - Cancer Research
JF - Cancer Research
IS - 13
ER -