Stimulatory effect of head and neck cancer cell lines on monocyte derived dendritic cells
(2020) KIMM05 20192Department of Immunotechnology
- Abstract
- Deeper understanding of the interactions between the immune system and tumour cells might hold the key of solving several problems regarding cancer. To increase our understanding of the functional properties of human immune cells within the tumour microenvironment, it is essential to develop relevant in vitro methods. Currently, there is lack of appropriate models for immune oncology studies, and the objective of this master thesis project was therefore to perform the first steps in combining antigen-presenting cells and tumour cells, and assess how culture media composition affected the phenotype of dendritic cells (DCs). Commonly used in vitro models to study cancer cells include 2D cell cultures and organoids, which are 3D formations... (More)
- Deeper understanding of the interactions between the immune system and tumour cells might hold the key of solving several problems regarding cancer. To increase our understanding of the functional properties of human immune cells within the tumour microenvironment, it is essential to develop relevant in vitro methods. Currently, there is lack of appropriate models for immune oncology studies, and the objective of this master thesis project was therefore to perform the first steps in combining antigen-presenting cells and tumour cells, and assess how culture media composition affected the phenotype of dendritic cells (DCs). Commonly used in vitro models to study cancer cells include 2D cell cultures and organoids, which are 3D formations mimicking the original tissue. These model systems can become even more useful in combination with other cell types to form co-cultures. In this study, we demonstrate that the supernatant from the head and neck cancer cell lines HN4 and HN26 have a stimulatory effect on monocyte-derived dendritic cells (moDCs). Two molecules involved in T-cell activation, CD86 and HLA-DR, were upregulated upon coculture with HN4 and HN26. The same stimulatory effect could be seen in 2D co-cultures with HN26 and moDCs. Furthermore, a preparatory experiment for future 3D co-cultures demonstrate that Matrigel, used for organoid formation, have a risk of activating moDCs. In conclusion, this project has discovered that HN4 and HN26 have an activating effect on moDCs and thereby, highlighted some challenges with future co-culturing projects. (Less)
- Popular Abstract
- Cancer is a devastating disease, caused by mutations in the cells and resulting in tumours that could be life threatening. Each tumour is unique and because of that there is a need for more individualised treatments to save more lives. One cancer type with few therapeutic options is head and neck cancer.
The immune system is responsible of keeping us healthy and protecting us against various threats from the outside or the inside of the body. But sometimes things go wrong and we get ill. Tumour cells have developed different strategies to suppress and avoid activation of anti-tumour immune responses. This allows them to grow and spread in the body. Investigating these interactions might hold a key to reversing it and teach the immune... (More) - Cancer is a devastating disease, caused by mutations in the cells and resulting in tumours that could be life threatening. Each tumour is unique and because of that there is a need for more individualised treatments to save more lives. One cancer type with few therapeutic options is head and neck cancer.
The immune system is responsible of keeping us healthy and protecting us against various threats from the outside or the inside of the body. But sometimes things go wrong and we get ill. Tumour cells have developed different strategies to suppress and avoid activation of anti-tumour immune responses. This allows them to grow and spread in the body. Investigating these interactions might hold a key to reversing it and teach the immune system how to fight the tumour cells.
Our current knowledge of cancer and the immune system comes from investigating tumours and using different animal models. The usage of animal models is controversial from an ethical point of view and further, even though animals share similarities with humans, some more than others, we are still too different from each other. Therefore, there is a need for new options to investigate cancer and one of these is to use a technique to grow cancer cells without the need of a body. By combining these tumour cells with immune cells isolated from blood it could be possible to study the interactions and to test new therapeutic options on.
In this study, the first objective was to investigate the effect of molecules produced by the tumour cells on human immune cells. Earlier studies have found that cancer cells change their environment which prevent the immune cells from responding to the threat like they normally would. However, in this study the immune cells could respond normally even after exposure to these molecules. To further test if direct contact between the same cancer cells and immune cells would disturb their normal behaviour another experiment was conducted. In this experiment, immune cells were added to cancer cells and the effects were measured. The results were the same, the immune cells could respond normally. Further research might explain why these specific cancer cells were unable to change the behaviour of the immune cells.
If future experiments with cancer types able to change the behaviour of the immune cells are successful, the next step would be to continue with 3D models of tumours and incorporate immune cells into the model. This would open the possibility to grow tumours from the patients’ own cancer cells and combine them with their immune cells to study the interactions and predicting if a treatment would be successful. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9003173
- author
- Svensson, Caroline LU
- supervisor
- organization
- course
- KIMM05 20192
- year
- 2020
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9003173
- date added to LUP
- 2020-01-28 15:11:30
- date last changed
- 2020-01-28 15:11:30
@misc{9003173,
abstract = {{Deeper understanding of the interactions between the immune system and tumour cells might hold the key of solving several problems regarding cancer. To increase our understanding of the functional properties of human immune cells within the tumour microenvironment, it is essential to develop relevant in vitro methods. Currently, there is lack of appropriate models for immune oncology studies, and the objective of this master thesis project was therefore to perform the first steps in combining antigen-presenting cells and tumour cells, and assess how culture media composition affected the phenotype of dendritic cells (DCs). Commonly used in vitro models to study cancer cells include 2D cell cultures and organoids, which are 3D formations mimicking the original tissue. These model systems can become even more useful in combination with other cell types to form co-cultures. In this study, we demonstrate that the supernatant from the head and neck cancer cell lines HN4 and HN26 have a stimulatory effect on monocyte-derived dendritic cells (moDCs). Two molecules involved in T-cell activation, CD86 and HLA-DR, were upregulated upon coculture with HN4 and HN26. The same stimulatory effect could be seen in 2D co-cultures with HN26 and moDCs. Furthermore, a preparatory experiment for future 3D co-cultures demonstrate that Matrigel, used for organoid formation, have a risk of activating moDCs. In conclusion, this project has discovered that HN4 and HN26 have an activating effect on moDCs and thereby, highlighted some challenges with future co-culturing projects.}},
author = {{Svensson, Caroline}},
language = {{eng}},
note = {{Student Paper}},
title = {{Stimulatory effect of head and neck cancer cell lines on monocyte derived dendritic cells}},
year = {{2020}},
}