Klinický význam molekul a procesů asociovaných s imunogenní buněčnou apoptózou v terapii nádorových onemocnění

Holíček, Peter

The clinical relevance of immunogenic cell death-associated signaling and molecules in cancer therapy The capacity of cancer cells to induce anticancer immune responses relies on multiple factors, including the antigenic repertoire of cancer cells and their ability to provide adjuvant signals, as represented by danger-associated molecular patterns (DAMPs), which are exposed and released by malignant cells during immunogenic cell death (ICD). The release and secretion of DAMPs can orchestrate the activation of innate and adaptive tumor-targeting immunity, resulting in tumor regression. Various chemotherapies, radiation therapy, physical modalities, and targeted anticancer agents have been described as potent ICD inducers, which besides being directly cytotoxic, can activate clinically relevant anticancer immune responses. Therefore, patients whose tumor microenvironment (TME) is shows defective DAMP release or downstream DAMP-sensing signaling pathways do not fully benefit from ICD-inducing treatments, which can lead to overall therapeutic failure. My dissertation contributes to this field by exploring the impact of ICD on the development of innate anticancer immune responses, with a particular focus on natural killer (NK) cells, showing that surface-exposed calreticulin (ecto-CALR) positively impacts the...

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