Carbonic anhydrase IX has chaperone-like functions and is an immunoadjuvant.
Carbonic anhydrase IX has chaperone-like functions and is an immunoadjuvant.
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DOI：
10.1158/1535-7163.mct-08-0603
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发表时间：
2008-12
影响因子：
5.7
通讯作者：
Kim HL
中科院分区：
文献类型：
--
作者：
Wang Y;Wang XY;Subjeck JR;Kim HL
Carbonic anhydrase IX (CA9) is a hypoxia-regulated, transmembrane protein associated with neoplastic growth in a large spectrum of human tumors. CA9 is expressed in nearly all clear cell renal tumors; levels of CA9 expression predict prognosis and response to IL2 therapy. These observations may be explained by a novel chaperone-like function of CA9, which allows it to serve as an immunoadjuvant and stimulate an adaptive immune response against tumor antigens. Classic heat shock proteins (HSPs) such as HSP110 and HSP70 are upregulated in response to cellular stress and function to protect intracellular proteins from aggregation. Similarly, CA9 formed complexes with client proteins and inhibited heat-induced aggregation, and enabled refolding of denatured client protein. HSPs released from injured cells activate an immune response. CA9 bound dendritic cells (DCs) in a receptor-specific manner. Bound CA9 was internalized by DCs and processed primarily through the proteosomal pathway. In murine melanoma model, a complex of CA9 and gp100 generated a gp100-specific antitumor response. A soluble form of CA9 shed from tumor cells had the same chaperone-like functions, providing renal tumors and hypoxic cells with a mechanism for stimulating an immune response against extracellular antigens. IL2 treatment of patient renal tumors in short-term culture increased CA9 shedding, suggesting a strategy for augmenting the immunogenicity of renal tumors. CA9 has chaperone-like functions and CA9 shed from tumors may play a direct role in stimulating an adaptive immune response.
