Tissue Specific Differentiation Antigens

Tumors may express molecules that are present only on the normal cells of origin and not on cells from other tissues. These antigens are called differentiation antigens because they are specific for particular lineages or differentiation stages of various cell types. Their importance is as potential targets for immunotherapy and for identification of the tissue of origin of tumors. For example, several melanoma antigens that are targets of CTLs in patients are melanocyte differentiation antigens, such as tyrosinase, mentioned earlier. Lymphomas may be diagnosed as B cell-derived tumors by the detection of surface markers characteristic of this lineage, such as CD10 (previously called common acute lymphoblastic leukemia antigen, or CALLA) and CD20. Antibodies against these molecules are also used for tumor immunotherapy; the most successful immunotherapy for non-Hodgkin's B cell lymphomas is an anti-CD20 antibody (rituximab). The idiotypic determinants of the surface Ig of a clonal B cell population are markers for that B cell clone because all other B cells express different idiotypes. Therefore, the Ig idiotype is a highly specific tumor antigen for B cell lymphomas and leukemias. These differentiation antigens are normal self molecules, and therefore they do not usually induce strong immune responses in tumor-bearing hosts.

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