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Immunotherapy is in its infancy for many diseases, whether they are neoplastic or autoimmune. The major issues for cancer immunotherapy today involve the definition of molecular targets and the generation of effector mechanisms to attack the targets of interest. Soft tissue sarcomas provide a unique opportunity to examine the immune response against defined antigens. Many types of sarcomas contain tumor-specific chromosomal translocations encoding fusion proteins, which are attractive targets for immunotherapy. Our understanding of the immune system is also coming into clearer focus with the discovery of dendritic cells as powerful natural adjuvants and the teasing out of mechanisms leading to immunity versus tolerance as examples. It is hoped that the intersection of cellular immunology and sarcoma molecular biology will lead to new modalities of therapy for this group of patients with this heterogeneous group of diseases.