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Cellular senescence and tumour immuno-surveillance
Včelková, Terézia ; Hodný, Zdeněk (advisor) ; Štěpánek, Ivan (referee)
Cellular senescence represents the antitumor mechanism that has been considered to be irreversible. However, it appears that under certain circumstances the cell is able to escape from senescent state, that led to increased risk of tumor transformation. Senescent cells secrete a plethora of substances including cytokines that modulate their surrounding environment. It turns out that they are able to induce senescence in neighboring cells and, paradoxically, they are the reason of tumor promoting effects of cellular senescence. According to the latest findings, senescent cells are subject to surveillance of the immune system, which is named as senescent surveillance. This event provide the ablation of these non- proliferating, damaged cells and protects the body from pathologies that are associated specifically with the phenomenon of cellular senescence. The aim of this bachelor thesis is to compile the current knowledge about the interactions of senescent cells with the immune system and to show their relevance in the war against cancer. Powered by TCPDF (www.tcpdf.org)
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Immunotherapy of HPV16 - associated cancers and regulation of antitumour immune response
Štěpánek, Ivan ; Reiniš, Milan (advisor) ; Lipoldová, Marie (referee) ; Němečková, Šárka (referee)
The MHC class I status of tumour cells during immunotherapy is often underestimated. It represents one of important tumour escape mechanisms and thus can contribute to the failure of most of the cancer clinical trials that are usually based on the induction of cytotoxic T cell responses. Epigenetic changes in the promoters of genes involved in the MHC class I Ag presentation can result in decreased expression of the cell surface MHC molecules on tumour cells. Thus, epigenetic modifiers can restore an expression of the MHC class I molecules and make tumours visible to the CD8+ effector cells. Besides the epigenetic changes on the tumour cells, epigenetic modulators affect cells of the immune system such as dendritic cells (DC). Tumour cells can escape from the immune response not only by changes in the cancer cells, but also by influencing, expanding and/or activating immunoregulatory cell populations, such as regulatory T cells (Treg). This thesis focuses on the potential of the DC-based vaccines against HPV-16-associated tumours with a different MHC class I expression, on the combination of cancer immunotherapy with the treatment using epigenetic modifiers, with special attention paid to their effects on DC, and, finally, on the impacts of the anti-CD25 antibody (used for Treg elimination) on Treg and NKT...
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