Heat shock proteins, tumor immunogenicity and antigen presentation: an integrated view

✍ Scribed by Andrew D. Wells; Miroslav Malkovsky

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 176 KB
• Volume: 21
• Category: Article
• ISSN: 0167-5699
• DOI: 10.1016/s0167-5699(99)01558-3

✦ Synopsis

umors pose a unique immunological problem in that they are not completely foreign entities, but rather are derived from tissues of the host. Nevertheless, early studies have shown that some autologous tumor cells possess antigens capable of inducing protective immunity (reviewed in Ref. 1). In general, tumors can be categorized as either immunogenic or nonimmunogenic, based on their ability to induce a measurable immune response. Some of these responses might be protective, and are most often mediated by T cells 2,3 . Consistent with these early findings, most tumor-associated antigens identified to date are major histocompatibility complex (MHC)-restricted T-cell epitopes derived from proteins that have undergone mutation during tumorigenesis, are normally expressed at a stage in embryogenesis preceding the development of the immune system or are abundant in cancerous tissue compared with normal tissue 4 .

T cells require two signals to become activated for optimal effector function: antigenic peptide in the context of MHC molecules, along with a costimulatory ligand interaction (reviewed in Ref. 5). Although this scenario might occur frequently in vivo, many tumors are either derived from tissues that do not normally present antigens and support T-cell activation, or have lost the capacity to do so as a result of mutation or downregulation of immunologically relevant molecules [6][7][8][9][10] . Consequently, most tumors are poorly immunogenic.