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Indexed/Abstracted in: EMBASE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 0,246
Online ISSN 1827-160X
Lollini P. L. 1, Bronte V. 2
1 Institute for Cancer Research, University of Bologna, Bologna, Italy;
2 Department of Oncology and Surgical Sciences, University of Padua, Padua, Italy
Mouse experimental models have unveiled important aspects of the interaction between tumors and host immune system. T and B lymphocytes can efficiently recognize antigens expressed by cancer cells but tumors display an array of strategies to restrain the immune attack. Genetic abnormalities typical of growing cancer often result in deregulated synthesis of cytokines that either paralyze the immune effectors or prevent their activation by tampering with the function and differentiation of antigen presenting cells. The effect of cytokines on the antitumor response is complex and, sometimes, contradictory. Tumor cells transduced with cytokine genes were used both as tools to analyze the antitumor response and as therapeutic vaccines. Morpholo-gical and functional studies revealed that the rejection of gene-transduced tumor cells is the common outcome of distinct immune responses elicited in the host by the products of different transgenes. Engineered tumor cells induced measurable responses, but usually did not lead to a complete eradication of pre-existing tumors. However, multiple gene combination significantly improved their therapeutic efficacy through the activation of synergistic immune effectors. As an alternative to whole cell vaccines, recombinant cancer vaccines are designed to target the immune response against a known tumor antigen. Recombinant cancer vaccines based on “self” antigens demonstrated the possibility to break tolerance and prime the immune system; the antitumor response that they elicited, however, could occasionally associate with autoimmune manifestations. The latest developments come from transgenic and knockout mice. A number of new immunodeficient mice allow a precise definition of the role played by components of the immune system in the response against tumors. Mice carrying induced mutations in oncogenes and in oncosuppressor genes are faithful models for reconstructing the tumor natural history. Recent studies demonstrated that genetically-determined carcinogenesis could be prevented by immunological maneuvers in mice, a new concept that awaits testing in humans.