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Semi-allogeneic vaccines and tumor-induced immune tolerance

DOI: 10.1186/1479-5876-7-3

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Almost a century has passed since Paul Erlich first proposed that the immune system has the potential to eradicate cancer even though tumor cells arise from normal cells. Fifty years later the immune surveillance theory put forth that lymphocytes have the capacity to survey and destroy newly arising tumor cells that continuously appear in the body [1]. The conviction that the immune system can be mobilized as well as manipulated to eradicate tumor cells has invigorated the field of tumor immunology, one of the most active fields in immunology. The parallel discoveries of histocompatibility antigens in humans and mice are a good example of how studies in animal models and humans may go hand in hand [2]. In fact, animal studies continue as a basis for important advances because they have allowed the evaluation of multiple parameters in tumor immunology that are not possible in clinical studies [3].Despite a reasonable understanding of anti-tumor effector mechanisms, clinical studies investigating spontaneous anti-tumor immune responses have yet to lead to reproducible or consistent tumor regression. Thus, the question of why tumors continue to grow and metastasize in immunological competent cancer patients remains unanswered. Several observations have demonstrated that tumors evade and actively suppress the immune system. Tumor evasion of the immune system, termed immune escape, may occur through several mechanisms, including (i) tolerance or anergy induction; (ii) the genetic instability of tumors; (iii) modulation of tumor antigens; and (iv) decreased major histocompatibility complex class I (MHC-I) expression [4]. In addition to evasion of the immune system, tumors actively suppress the immune system directly through production of immune suppressive cytokines and indirectly through the induction of immune inhibitory cells [5]. This secretion of soluble factors is thought to contribute to the Th2-skewed immune responses observed in cancer patients and to induce the


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