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Tumor Cell Resistance to Apoptosis by Infi ltrating Cytotoxic Lymphocytes

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Book cover Innate and Adaptive Immunity in the Tumor Microenvironment

Part of the book series: The Tumor Microenvironment ((TTME,volume 1))

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Cancer patients have been treated with conventional chemotherapy, radiation, and hormonal therapy with significant clinical responses. However, patients develop resistance and they no longer respond to the above therapies. Immunotherapy has been considered as an alternative approach to overcome resistance and several antibody-mediated new cell-mediated therapies have been introduced and yielded significant clinical responses. The development of cell mediated antitumor cytotoxic immunotherapy has also advanced significantly with the design of numerous strategies to generate a specific antitumor cytotoxic response. However, the clinical response with cytotoxic immunotherapy remains poor and several proposed mechanisms have been suggested for the poor response. One mechanism that received little attention is the development of tumor cell resistance to cytotoxic stimuli, including both antibody-mediated and cell-mediated. The resistance, inherent or acquired, primarily results from the dysregulation of apoptotic pathways in the tumor cells and thus rendering them refractory to apoptotic stimuli including chemotherapy, radiation, and immunotherapy. The development of cross-resistance to apoptosis may play an important role in the poor clinical response observed in patients with a strong cytotoxic immune system. The molecular understanding of immune resistance identified many targets whose modifications by selective sensitizing agents reversed resistance. Such sensitizing agents included low concentrations of chemotherapeutic drugs, chemical and pharmacological inhibitors of survival pathways, anti-receptor antibodies, siRNA, cytokines, etc. Such sensitizing agents when used in combination with immunotherapy reversed immune resistance. In addition, the tumor microenvironment is regulated by infiltrating cells and the secretion of several factors that regulate tumor cell sensitivity to killing. Agents that can interfere with these factors should potentiate the reversal of immune resistance.

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  1. Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Benjamin Bonavida

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  1. Lautenberg Center for General and Tumor Immunology, Hebrew University—Hadassah Medical School, Jerusalem, Israel

    Eitan Yefenof

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Bonavida, B. (2008). Tumor Cell Resistance to Apoptosis by Infi ltrating Cytotoxic Lymphocytes. In: Yefenof, E. (eds) Innate and Adaptive Immunity in the Tumor Microenvironment. The Tumor Microenvironment, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6750-1_6

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