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Tumor immunity via homeostatic T cell proliferation: mechanistic aspects and clinical perspectives

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Abstract

Efforts to develop effective anti-tumor immunotherapies are hampered by the difficulty of overcoming tolerance against tumor antigens, which in most instances are normal gene products that are over-expressed, preferentially expressed or re-expressed in cancer cells. Considering that lymphopenia-induced homeostatic T cell proliferation is mediated by self-peptide/MHC recognition and that the expanded cells acquire some effector functions, we hypothesized that this process could be used to break tolerance against tumor antigens. Studies by us and others in several mouse models demonstrated that availability of tumor antigens during homeostatic T cell proliferation indeed leads to effective anti-tumor autoimmunity with specificity and memory. This effect appears to be mediated by reduction in the activation threshold of low-affinity tumor-specific T cells, leading to their preferential engagement and expansion. In its simplicity, this approach is likely to have application in humans, since it relies on conventional lymphopenia-inducing cancer therapies, infusion of autologous lymphocytes and, optimally, tumor-specific vaccination.

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Acknowledgements

This is publication number 17145-IMM from the Department of Immunology of The Scripps Research Institute. The work of the authors reported herein was supported in part by U.S. Public Health Service Grants (AR32103, AR39555, AI32751, AI52257) and the Department of Defense Breast Cancer Research Program (W81XWH-04-1-0454). The authors thank M. Kat Occhipinti-Bender for editorial assistance.

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  1. Department of Immunology, IMM-3, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Roberto Baccala, Rosana Gonzalez-Quintial & Argyrios N. Theofilopoulos

  2. Genentech Inc., 1 DNA Way, S. San Francisco, CA, 94080, USA

    Wolfgang Dummer

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  1. Roberto Baccala
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  2. Rosana Gonzalez-Quintial
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  3. Wolfgang Dummer
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  4. Argyrios N. Theofilopoulos
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Correspondence to Roberto Baccala.

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Baccala, R., Gonzalez-Quintial, R., Dummer, W. et al. Tumor immunity via homeostatic T cell proliferation: mechanistic aspects and clinical perspectives. Springer Semin Immun 27, 75–85 (2005). https://doi.org/10.1007/s00281-004-0196-9

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  • DOI: https://doi.org/10.1007/s00281-004-0196-9

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