Secretion of Tumor-Specific Antigen by Myeloma Cells Is Required for Cancer Immunosurveillance by CD4+ T Cells

被引:42
作者
Corthay, Alexandre
Lundin, Katrin U.
Lorvik, Kristina Berg
Hofgaard, Peter O.
Bogen, Bjarne
机构
[1] Univ Oslo, Inst Immunol, Ctr Immune Regulat, Oslo, Norway
[2] Univ Oslo, Rikshosp, Oslo Univ Hosp, N-0027 Oslo, Norway
关键词
COMPLEX CLASS-II; IN-VIVO; IMMUNOGLOBULIN IDIOTYPE; DENDRITIC CELLS; LYMPHOCYTES; PLASMACYTOMA; POPULATIONS; THYMOCYTES; RESISTANCE; EXPRESSION;
D O I
10.1158/0008-5472.CAN-08-4816
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Tumor-specific CD4(+) T cells orchestrate the adaptive immune responses against cancer. We have previously shown that CD4(+) T cells recognize MHC class II-negative myeloma cells indirectly by collaborating with tumor-infiltrating macrophages. We, here, hypothesize that this critical step may be dependent on secretion of tumor-specific antigens by cancer cells. This was investigated using T-cell receptor-transgenic mice, in which CD4(+) T cells mediate rejection of syngeneic MOPC315 myeloma cells. We analyzed the immune response against myeloma cell variants, which either secrete or retain intracellularly a tumor-specific idiotypic (Id) antigen. Our results reveal that CD4(+) T cells helped by macrophages are capable of detecting nonsecreted tumor antigens from MHC class II-negative cancer cells. However, Id secretion was required for successful myeloma immunosurveillance. Antigen secretion resulted in stronger priming of naive myeloma-specific CD4(+) T cells in tumor-draining lymph nodes. Secretion of antigen by at least some cancer cells within a tumor was shown to facilitate immunosurveillance. Treatment by local injection of purified tumor-specific antigen successfully enhanced immunity against nonsecreting myeloma cells. Collectively, the data indicate that antigen concentration within the tumor extracellular matrix must reach a certain threshold to allow successful cancer immunosurveillance by CD4(+) T cells. [Cancer Res 2009;69(14):5901-7]
引用
收藏
页码:5901 / 5907
页数:7
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