CD40-activated apoptotic tumor cell-pulsed dendritic cell could potentially elicit antitumor immune response: involvement of up-regulation of B7-H3 expression.
Dendritic cells (DCs) initiate and direct immune responses. Previous in vitro and in vivo studies have showed that DCs matured with CD40 linking signal could potentially elicit and boost antitumor immunity, however, its molecular mechanism remain elusive. This study demonstrates that expression of B7-H3 on apoptotic cell-loading DCs is up-regulated markedly by CD40 activation but not by tumor necrosis factor-alpha stimulation. There was no significant difference found with CD40, CD80, or CD86 expressions when activated by CD40 or tumor necrosis factor-alpha stimulation. In tumor-bearing mice, T cells conditioned with B7-H3-blocked on CD40-activated apoptotic tumor cell-pulsed DCs had a decreased ability to inhibit tumor growth. Therefore, it is hypothesized that high levels of B7-H3 expression contributes to the ability of CD40-activated tumor associated DCs in eliciting efficient antitumor immune response, given this fact the potentially significant clinical implications, CD40-activated DCs merit further considerations when preparing DCs for clinical application.
Chen
Cheng
C
Clinical Immunology Laboratory of Jiangsu Province, The First Affiliated Hospital of Soochow University, Suzhou, China.
Zhu
Yi-Bei
YB
Qu
Qiu-Xia
QX
Ge
Yan
Y
Huang
Jian-An
JA
Wang
Yong
Y
Zhang
Xue-Guang
XG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000970:Antineoplastic Agents; D060887:B7 Antigens; D018122:B7-1 Antigen; D019013:CD40 Antigens; C486038:Cd276 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin