TY - JOUR
T1 - Lentivector prime and vaccinia virus vector boost generate high-quality CD8 memory T cells and prevent autochthonous mouse melanoma
AU - Xiao, Haiyan
AU - Peng, Yibing
AU - Hong, Yuan
AU - Liu, Yanjun
AU - Guo, Z. Sheng
AU - Bartlett, David L.
AU - Fu, Ning
AU - He, Yukai
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/8/15
Y1 - 2011/8/15
N2 - Most cancer vaccines, to date, fail to control established tumors. However, their application in preventing tumors is another question that is understudied. In the current study, we investigated the CD8 memory T cell responses of lentivector (lv) immunization and its potential to prevent melanoma using both transplantable B16 tumor and autochthonous melanoma models. We found that lv-expressing xenogenic human gp100 could induce potent CD8 responses that cross-react with mouse gp100. Importantly, the lvprimed CD8 response consisted of a high number of memory precursors and could be further increased by recombinant vaccinia virus vector (vv) boost, resulting in enhanced CD8 memory response. These long-lasting CD8 memory T cells played a critical role in immune surveillance and could rapidly respond and expand after sensing B16 tumor cells to prevent tumor establishment. Although CD8 response plays a dominant role after lv immunization, both CD4 and CD8 T cells are responsible for the immune prevention. In addition, we surprisingly found that CD4 help was not only critical for generating primary CD8 responses, but also important for secondary CD8 responses of vv boost. CD4 depletion prior to lv prime or prior to vv boost substantially reduced the magnitude of secondary CD8 effector and memory responses, and severely compromised the effect of cancer immune prevention. More importantly, the CD8 memory response from lv-vv prime-boost immunization could effectively prevent autochthonous melanoma in tumor-prone transgenic mice, providing a strong evidence that lv-vv prime-boost strategy is an effective approach for cancer immune prevention.
AB - Most cancer vaccines, to date, fail to control established tumors. However, their application in preventing tumors is another question that is understudied. In the current study, we investigated the CD8 memory T cell responses of lentivector (lv) immunization and its potential to prevent melanoma using both transplantable B16 tumor and autochthonous melanoma models. We found that lv-expressing xenogenic human gp100 could induce potent CD8 responses that cross-react with mouse gp100. Importantly, the lvprimed CD8 response consisted of a high number of memory precursors and could be further increased by recombinant vaccinia virus vector (vv) boost, resulting in enhanced CD8 memory response. These long-lasting CD8 memory T cells played a critical role in immune surveillance and could rapidly respond and expand after sensing B16 tumor cells to prevent tumor establishment. Although CD8 response plays a dominant role after lv immunization, both CD4 and CD8 T cells are responsible for the immune prevention. In addition, we surprisingly found that CD4 help was not only critical for generating primary CD8 responses, but also important for secondary CD8 responses of vv boost. CD4 depletion prior to lv prime or prior to vv boost substantially reduced the magnitude of secondary CD8 effector and memory responses, and severely compromised the effect of cancer immune prevention. More importantly, the CD8 memory response from lv-vv prime-boost immunization could effectively prevent autochthonous melanoma in tumor-prone transgenic mice, providing a strong evidence that lv-vv prime-boost strategy is an effective approach for cancer immune prevention.
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U2 - 10.4049/jimmunol.1101138
DO - 10.4049/jimmunol.1101138
M3 - Article
C2 - 21746967
AN - SCOPUS:80051921852
SN - 0022-1767
VL - 187
SP - 1788
EP - 1796
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -