Universität zu Köln

Niu, Lina (2025). Regulation of Vascular Endothelial Cells and Cytokines in the Tumor Microenvironment by Radiotherapy. PhD thesis, Universität zu Köln.

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Abstract

Cancer is still an essential threat to human health. In recent decades, research on the treatment of tumors has made great progress. Surgery, radiotherapy (RT) and chemotherapy (CT) are traditional cancer treatments. In addition, with the development of scientific research and the deepening of the understanding of the molecular level, research on cancer treatment at the molecular level is becoming one of the most important directions, and immunotherapy has become a milestone in cancer treatment. Surgery, RT and CT are aimed at directly killing malignant cells, while immunotherapy mainly achieves the purpose of destroying cancer cells by eliminating the tumor's immune escape and activating the host's immune response. Although great breakthroughs and progress have been made in cancer treatments over the years, cancer remains one of the biggest threats to people's health. Since rays were discovered to damage the deoxyribonucleic acid (DNA) of cells and were used to kill cancer cells and control the growth of tumors, RT technology has been constantly innovating with the development of science and technology. From conventional radiotherapy to intensity modulated radiotherapy (IMRT), and from external radiotherapy to brachytherapy and particle implantation, the accuracy, safety and effectiveness of radiotherapy are constantly improving. However, due to the unlimited proliferation nature of cancer cells, cancer always becomes resistant to treatments and cancer cells continue to grow. Since immunotherapy was applied to clinical treatment, a milestone breakthrough was made in tumor treatment. However, what is confusing is that many patients still cannot benefit from immunotherapy. It is worth noting that clinical studies have found that the therapeutic effect of combined RT and immunotherapy is better than that of immunotherapy alone, and even some patients who do not respond to immunotherapy can benefit from immunotherapy after receiving combined RT and immunotherapy. Compared with single treatment, combination therapy often achieves better results, and RT, CT and surgery are often used in combination treatment. However, the difference is that the combination of RT, CT and surgery mainly depends on the superposition effect of different treatment methods on the killing of malignant cells, while the promotion of RT and immunotherapy combined therapy may affect the immune response system, which is a direction worthy of exploration. Activation of anti-tumor immune response requires activation of the immune system to recognize tumor antigens and activated immune cells to migrate across the endothelium to the location of cancer cells to exert immune effects. Immunotherapy, such as checkpoint inhibitors, can prevent cancer from escaping the immune system and reactivate the immune system's response to malignant cells. Some patients do not respond to immunotherapy alone, but benefit from the combination of immunotherapy and RT. We speculate that one reason for this phenomenon may be that RT can change the tumor microenvironment (TME) and promote the transendothelial migration (TEM) of immune cells. The TME is one of the most important areas of tumor treatment research, including the aggregation and migration of immune cells, the dysfunction and activation of vascular endothelial cells, and various cytokines such as TNF-α, IFN-γ, IL-6, etc. Therefore, the activation of vascular endothelial cells (ECs) is very important for cancer immunotherapy, and the adhesion molecules such as P-selectin, E-selectin, ICAM1 and VCAM1 on the surface of vascular endothelium play a critical role in the process of TEM of immune cells. In this thesis, I investigated the influence of RT on the TME especially on the regulation of adhesion molecules expressed on the surface of vascular ECs through in vivo and in vitro experiments. The results showed that RT upregulated the expression levels of E-selectin, P-selectin, ICAM1 and VCAM1 on ECs, and also upregulated the levels of some inflammatory cytokines GM-CSF, IL-1α and IL-1β. The upregulation of vascular endothelial adhesion receptors and inflammatory cytokines may be the targets and new points for the study of combination therapy with RT and immunotherapy.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Niu, Lina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-790692
Date:	2025
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Strahlentherapie > Klinik und Poliklinik für Strahlentherapie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language cancer English radiotherapy English endothelial cells English
Date of oral exam:	29 August 2025
Referee:	Name Academic Title Her, Jan Privatdozent Dr. med. Pallasch, Christian Universitätsprofessor Dr. med.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79069