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Matches in Ghent University Academic Bibliography for { <https://biblio.ugent.be/publication/01J8J4XWZ18KKY91ATKXK2ZVSS> ?p ?o. }

• 01J8J4XWZ18KKY91ATKXK2ZVSS classification D1.
• 01J8J4XWZ18KKY91ATKXK2ZVSS promoter 3AEA5496-F0EE-11E1-A9DE-61C894A0A6B4.
• 01J8J4XWZ18KKY91ATKXK2ZVSS promoter F6642C16-F0ED-11E1-A9DE-61C894A0A6B4.
• 01J8J4XWZ18KKY91ATKXK2ZVSS date "2024".
• 01J8J4XWZ18KKY91ATKXK2ZVSS language "eng".
• 01J8J4XWZ18KKY91ATKXK2ZVSS type dissertation.
• 01J8J4XWZ18KKY91ATKXK2ZVSS hasPart urn:uuid:d10a460b-7379-476e-beb9-7501cfc9dbd4.
• 01J8J4XWZ18KKY91ATKXK2ZVSS subject "Medicine and Health Sciences".
• 01J8J4XWZ18KKY91ATKXK2ZVSS abstract "Enhancing and educating our body's immune system is undoubtedly one of the paramount objectives in the design of efficient cancer treatments. Traditional cancer therapies like chemotherapy and γ-radiation primarily aim to kill cancer cells directly. However, these treatments often come with significant side effects and may not fully engage the immune system in tackling cancer. Cancer immunotherapy stands as a revolutionary approach in combating cancer, leveraging the body's immune system to target and eliminate malignant cells. Central to this strategy is the concept of immunogenic cell death (ICD), where cancer cells succumb to treatment in a manner that triggers an immune response against the cancer. ICD operates through a dual mechanism: firstly, cancer cells are directly targeted and eliminated by various therapeutic agents or therapeutic modalities, and secondly, the dying cancer cells release immunostimulatory signals such as damage-associated molecular patterns (DAMPs) and, in combination with tumor association antigens (TAAs), induce a strong anti-cancer immunity leading to eradication of the cancer and generation of long-lasting immunological memory preventing the cancer relapse. Various therapeutic modalities have been shown to induce ICD in both murine and human cancer cell lines in vitro. Moreover, their immunogenic potential has been demonstrated in tumor therapeutic and vaccination models in mice in vivo. Most importantly, ICD-inducing agents and therapies have been already admitted into the clinics and are used for the treatment of cancer in patients. There is a persistent challenge in cancer therapy being the development of drug resistance and immune evasion mechanisms, allowing cancer cells to withstand various forms of anti-cancer therapy and targeted therapies. The way cancer cells die influences the body's anti-cancer immunity, which plays a role in the effectiveness of cancer treatments and the prolonged survival of patients. While many agents triggering immunogenic apoptosis or necroptosis in cancer cells can stimulate anti-cancer immune responses, yet resistance to these forms of cell death is frequently encountered. Consequently, identifying alternative methods for eliminating cancer cells is critically important. As a result, there is a pressing need for alternative therapeutic modalities capable of overcoming the cell death resistance displayed by cancer cells. Among the emerging types of ICD, ferroptosis offers notable advantages over apoptosis and necroptosis. Ferroptosis, distinct in both morphology and biochemistry from apoptosis and necroptosis, offers an alternative strategy for targeting resistant cancers. Ferroptosis leads to lipid peroxidation via abnormal iron metabolism, which can overcome previously mentioned cell death resistance and more effectively induce anti-cancer immunity leading to more potent cancer eradication. At the beginning of the PhD thesis, it was not known whether ferroptotic cancer cells are immunogenic. In the initial part of this study, our objective was to assess the immunogenic properties of cancer cells undergoing ferroptotic cell death. To achieve this, we utilized a murine MCA205 fibrosarcoma cell line commonly employed in ICD studies. Our findings reveal that only early (1h and 3h cell death induction) and not late (24h cell death induction) ferroptotic MCA205 cells release DAMPs (ATP and HMGB1) and activate bone marrow derived dendritic cells (CD11c+CD86+, CD11c+CD80+, CD11c+MHCII+, IL-6) in vitro. Upon immunization of mice with early ferroptotic cancer cells, we observed efficient anti-tumor protection against the challenge with viable cancer cells in immune-competent mice but not in Rag-2-/- mice suggesting that the 18 mechanism of immunogenicity is tightly regulated by the adaptive immune system and is time dependent. This contrasts with cancer cells undergoing freeze-thaw-induced accidental necrosis, which fail to elicit an efficient anti-cancer immune response. This work demonstrated that cancer cells in the early time-points of ferroptosis are immunogenic in vitro and in vivo. In the second part of the PhD thesis, we focused on potential strategies to modulate the interaction of late ferroptotic cancer cells with the cells of the immune system, more specifically, macrophages. An approach applying nanomaterials was selected which is based on the coating of late ferroptotic cancer cells with biopolymers by the Layer-by-Layer (LbL) method. As a primary step of the analysis, changes in mechanobiological properties of late ferroptotic cancer cells after the coating were measured by atomic force microscopy (AFM) and, in the next step, utilized to gain further understanding of the interaction between ferroptotic cancer cells and bone marrow derived macrophages. This work revealed that enhancing the elasticity of late ferroptotic cancer cells through LbL coatings led to increased uptake by macrophages (i.e., efferocytosis). The findings presented in this study highlight the significance of mechanobiological characteristics of dying cancer cells in the process of efferocytosis. Furthermore, these results offer promising prospects for nanomaterial-based therapeutic applications to increase the efferocytosis of dying cancer cells and thereby improve their adjuvanticity and anti-cancer immunity. Overall, our work opens new avenues for creating cancer treatment modalities that focus on triggering ferroptosis. Moreover, the work presented in the second part of the PhD thesis highlights the importance of the mechanobiology of ferroptotic cancer cells in controlling how macrophages engulf them, a process known as efferocytosis. This insight not only expands our understanding of immunogenic cell death but can be leveraged to create new therapeutic approaches for conditions where altering efferocytosis could be advantageous, as well as in the development of drug delivery mechanisms for cancer treatment.".
• 01J8J4XWZ18KKY91ATKXK2ZVSS author D7982FEC-D0C7-11E8-97EF-09125707D3EF.
• 01J8J4XWZ18KKY91ATKXK2ZVSS dateCreated "2024-09-24T13:53:27Z".
• 01J8J4XWZ18KKY91ATKXK2ZVSS dateModified "2024-11-28T00:16:39Z".
• 01J8J4XWZ18KKY91ATKXK2ZVSS name "IRONic cell death : unveiling the immunogenicity and efferocytosis of ferroptosis in cancer".
• 01J8J4XWZ18KKY91ATKXK2ZVSS pagination urn:uuid:89092691-5219-4835-9aba-b0932bb17d75.
• 01J8J4XWZ18KKY91ATKXK2ZVSS publisher urn:uuid:ca7e1aac-8730-49b7-9d95-8c66c3f34510.
• 01J8J4XWZ18KKY91ATKXK2ZVSS sameAs LU-01J8J4XWZ18KKY91ATKXK2ZVSS.
• 01J8J4XWZ18KKY91ATKXK2ZVSS sourceOrganization urn:uuid:57cba503-e0c9-45ba-bf48-aa2b7fc5b5cb.
• 01J8J4XWZ18KKY91ATKXK2ZVSS sourceOrganization urn:uuid:c23c566d-35fb-4508-a252-49ed76791d78.
• 01J8J4XWZ18KKY91ATKXK2ZVSS type D1.