Cancer immunosurveillance and immunoediting hypothesis

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Cancer immunosurveillance and immunoediting in humans, ways to improve immunogenicity of tumor cells and to design better immunotherapy protocols

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Toll-like receptory Transmembránové receptory I. typu extracelulární doména bohatá na leucin intracelulární Toll/IL-1 receptor (TIR) doména

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Copyright ©2005 Rockefeller University PressCasanova, J.-L. et al. J. Exp. Med. 2005;202:197-201Mortality curves at various periods of human historyImprovement of hygiene, beginning in the mid–19th century (preventing the transmission of infection) Introduction of vaccines, beginning in the late 19th century (preventing disease in infected individuals) Development of anti-infectious drugs, beginning in the early 20th century (preventing death in patients with clinical disease).

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1957- formulation of the cancer immunosurveillance hypothesis proposed by Thomas and Burnet: “sentinel thymus dependent cells of the body constantly surveyed host tissues for nascent transformed cells”

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Copyright ©1998 by the National Academy of SciencesKaplan, Daniel H. et al. (1998) Proc. Natl. Acad. Sci. USA 95, 7556-7561Role of IFNg in protection against cancer

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Dunn et al. Nature Reviews Immunology 6, 836–848 (November 2006) | doi:10.1038/nri1961

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immune system is capable of early recognition and elimination of cell in the process of malignant transformation mediated by various components of the immune system (T-cells, NKT cells, NK cells) scarce evidence for its existence in humansCancer immunosurveillance and immunoediting hypothesis

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GP Dunn, Immunity, 2004Cancer immunosurveillance and immunoediting hypothesisProtection no diseasePreneoplasiaNeoplasia

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Dhodapkar M., JEM, 2003Tumor cell specific enrichment of IFNg producing T cells in the bone marrow of patients with MGUS

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Infiltration of tumor tissue by T cells predicts better prognosis in colon cancer

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Infiltration of tumor tissue by T cells predicts better prognosis in colon cancer

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Infiltration of tumor tissue by T cells predicts better prognosis in colon cancer

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Factors inhibiting anti-tumor immune response

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Strategies to enhance anti-tumor immune response

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Cell surface calreticulin expression is a marker of immunogenic cell death

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Cell surface calreticulin expression is a marker of immunogenic cell death

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Bortezomib induces immunogenic cell death in myeloma cells

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ER resident chaperonesAnnexin V moleculesBortezomib anthracyclinsImmunityToleranceActivated dendritic cellImmature dendritic cellOther chemotherapeuticsImmunogenic cell deathNon-immunogenic cell deathTumor cellŠpíšek, R., Cell cycle, 2007

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Signals of immunogenic cell deathCell death inductionCalreticulin translocationHSP90 translocationHMGB1 releaseUric acid, ATP

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Last Updated: 8th March 2018