In vitro studies on the impact of irradiated head and neck squamous cell carcinoma cells on the differentiation of human monocytes to macrophages
Year: 2019
Type: dissertation
Abstract: BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common tumor diseases worldwide.Risk factors are alcohol and tobacco consume or infection with a high-risk human papillomavirus (HPV)-type.Patients with HPV+ status respond better to radiotherapy (RT), but the causal biological processes are not yet fully understood.HNSCC is treated with normofractionated RT, but in the last decade hypofractionated RT came into the focus of research and therapy.It is of interest to determine which cell death forms tumor cells undergo after normo-or hypofractionated RT, as the latter can lead to different immunological responses.Also, senescence, a stressinduced form of cell cycle arrest, also after RT, is predicted to have high influence on the immune system.In addition to that, we were interested in how the HPV-status impacts this.Furthermore, the potential of supernatants of treated tumor cells to impact on macrophage phenotype was examined, since the tumor microenvironment has been demonstrated to be strongly involved in therapy-induced anti-tumor immune reactions.Macrophages are part of the innate immune system and develop out of monocytes.They play an important role in the interaction of tumors cells with the immune system.Tumors utilize macrophages for angiogenesis and to expand.These infiltrating macrophages are called "tumor-associated macrophages" (TAM) and correlate with a poor outcome.It is known that there are more pro-inflammatory phenotypes (M1) and more anti-inflammatory phenotypes (M2).TAMs are more similar to the M2-phenotype.But as macrophages have high plasticity, the phenotype should be regarded as an indication only for pro-or anti-inflammatory reactions. MethodsIn vitro experiments were carried out with four human HNSCC cell lines of which two are bearing the HP virus and two are not.Cells were seeded and treated with X-Rays either normo-(5x2Gy) or hypofractionated (2x5Gy).Two days and six days after last fraction of RT, cells were analyzed regarding their Conclusion and outlookOur results confirm that macrophages have high plasticity in their phenotype in the tumor microenvironment, which seems to be individually influenced by RT.This also confirms that in HNSCC the different and individual interactions between the immune system and the tumor have to be taken into account.In future experiments the impact of both, tumor cell supernatant and the tumor cells themselves on macrophage phenotype, should be examined.
Author: Wild, Kristina
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7062480485