Differential expression of CSCs biomarkers in renal cell carcinoma stem cells after a combined treatment with phytochemicals and immune checkpoint inhibitors

Lyu, Chen (2024): Differential expression of CSCs biomarkers in renal cell carcinoma stem cells after a combined treatment with phytochemicals and immune checkpoint inhibitors. Dissertation, LMU München: Medizinische Fakultät

Abstract

Renal cell carcinoma (RCC) is a kind of kidney tumor that is distinguished by its tendency to stay undetected until late stages, resulting in a large rise in fatality rates. Immune checkpoint inhibitors have demonstrated potential in treating advanced RCC, either replacing or supplementing therapies with tyrosine kinase inhibitors (TKIs), with objective response rates varying from 42% to 71% for each combination regimen [1]. Not all patients respond to these therapies, only a few people with the median progression-free survival (PFS) varying from 11.6 to 15.4 months, followed by the therapy-resistance, which highlights the need for novel treatment strategies [2]. Recent studies have focused on the function of cancer stem cells (CSCs) in the development and progression of RCC, as these cells are thought to be resistant to traditional cancer therapies and contribute to tumor relapse. CSCs are a small subset of cells seen within malignancies that possess self-renewal and differentiation capabilities and are successful of initiating and sustaining tumor growth. CSCs have been recognized in more than a few cancers, together with RCC, and are related with in favorable outcomes. Therefore, figuring out CSC-specific biomarkers and growing treatments focused on these cells is necessary for enhancing affected person outcomes. One possible method for concentrated on CSCs in RCC is via the use of phytochemicals (PTCs), which are naturally happening compounds discovered in plants. PTCs have been proven to have anti-cancer properties, and some have been proven to mainly target CSCs. Therefore, there is developing amount of research in creating phytochemical-based treatment strategies for RCC that especially target CSCs. The goal of this thesis was to uncover new phytochemicals that originate from conventional herbs that target RCC CSCs, and combination with other treatments such as immune checkpoint inhibitor for enhancing the efficacy of present treatment strategies and creating new remedies for RCC. Various techniques, including viability, proliferation, migration, invasion, and apoptosis assays, have been utilized to identify promising candidate phytochemicals. Because of its exceptional ability to efficiently suppress cancer stem cells (CSCs), shikonin was chosen as the most promising and favorable partner for combination treatment with immune checkpoint inhibitors. Then, potential mechanisms of shikonin and ipilimumab involved in regulating T cell subpopulations and potential immunotherapeutic targets were investigated. Furthermore, figuring out biomarkers such as VCMA1 that predict response to immune checkpoint inhibitor remedy will permit for the improvement of personalized therapy plans for RCC patients.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 11. März 2024
• 1. Bericht­erstatter:in: Pohla, Heike