Spatial Multiplex Analysis of Immune Cell Infiltration in Mantle Cell Lymphoma
(2020) KIMM05 20192Department of Immunotechnology
- Abstract
- The tumour microenvironment in Mantle Cell Lymphoma (MCL) is underexplored. Through advancing understanding, it would be possible to stratify patients to the optimal immunotherapy. To enable analysis of more complex phenotypes, compared to single immunohistochemistry (IHC) staining, the aim of this thesis was to evaluate the novel overlay-analysis tool in HALO® using diagnostic MCL. This novel module enabled multiplex analysis and detection of colocalized immune cells, by overlaying images of individually stained IHC slides. The present study was restricted to CD3+ T lymphocytes, and the analysis of CD4, CD8, CD25, FoxP3, T-bet, GATA3, PD-1 and PD-L1 expression. Major technical limitations were identified associated with the overlay... (More)
- The tumour microenvironment in Mantle Cell Lymphoma (MCL) is underexplored. Through advancing understanding, it would be possible to stratify patients to the optimal immunotherapy. To enable analysis of more complex phenotypes, compared to single immunohistochemistry (IHC) staining, the aim of this thesis was to evaluate the novel overlay-analysis tool in HALO® using diagnostic MCL. This novel module enabled multiplex analysis and detection of colocalized immune cells, by overlaying images of individually stained IHC slides. The present study was restricted to CD3+ T lymphocytes, and the analysis of CD4, CD8, CD25, FoxP3, T-bet, GATA3, PD-1 and PD-L1 expression. Major technical limitations were identified associated with the overlay functionality in HALO®, and only part of the cohort could be used to draw conclusions related to biology. However, we could determine the frequency of sub-populations of T cells and show that, when the T cell associated markers (CD3, CD4 and CD8) are expressed in close proximity to FoxP3 or PD-L1, it pin-points a small subpopulation of high-risk patients. (Less)
- Popular Abstract
- Can digital analysis of patient tissue improve understanding of cancer?
Cancer is the second leading cause of death globally, according to WHO. Everyone is afflicted directly or indirectly. Even though the number of deaths caused by cancer is still increasing, the death rate is decreasing, thanks to advancing treatments. To be able to combat and treat the patients, we need a deeper understanding about the different diseases, that collectively are called cancer. With this study I use digital images, to determine the composition of immune cells in tumours from cancer patients.
In my project I used a software, HALO®, to analyse tumours in lymph nodes caused by a blood cancer called Mantle Cell Lymphoma. It is an aggressive type of... (More) - Can digital analysis of patient tissue improve understanding of cancer?
Cancer is the second leading cause of death globally, according to WHO. Everyone is afflicted directly or indirectly. Even though the number of deaths caused by cancer is still increasing, the death rate is decreasing, thanks to advancing treatments. To be able to combat and treat the patients, we need a deeper understanding about the different diseases, that collectively are called cancer. With this study I use digital images, to determine the composition of immune cells in tumours from cancer patients.
In my project I used a software, HALO®, to analyse tumours in lymph nodes caused by a blood cancer called Mantle Cell Lymphoma. It is an aggressive type of cancer that effects mostly elderly patients. Median survival is only 3-5 years. This cancer arises from abnormal cell growth of one type of immune cells. Immune cells are a part of the immune system and these cells are specialised on different tasks. Its function is to keep us healthy and kill all unnatural events, such as cancer or intruding bacteria, without attacking our own body. These immune cells are also present in the environment surrounding the tumour, but they are not able to kill the tumour cells in an established tumour. This surrounding environment has an impact on cancer growth and treatment response. By knowing which immune cells are present in the tumour, we hope to be able to personalise treatment to better fit each patient. As this cancer is very aggressive, the treatment is harsh and toxic for the patient. It would, therefore, be very beneficial to use a treatment option that utilise the body’s own immune system, called immunotherapy. Immunotherapy activates the immune system so it can kill the cancer cells. The tumours were collected from patients that participated in a clinical trial for a new therapy strategy. To analyse the tumour samples, I used a recently launched software and evaluated its potential to find the different immune cells in the tumour. The surface of the immune cells has different markers that allows us to distinguish the different types of immune cells. These markers can be stained with different colours. This way, the tumour samples were first stained, which made it possible to count them in the software. Then, the number of counted cells, stained with different markers, indicates which type of immune cells that are present in the tumour. The number of immune cells were different for each patient and therefore, I also compared the counted immune cells with how long the patients survived. I could see that patients with a high level of cells that have a marker called FoxP3 or PD-L1, which are related to suppression of the immune system, seems to have shorter survival or a more aggressive form of the cancer.
Overall, the new software had technical limitations leading to that not all patient samples could be analysed. The project was still able to give detailed information about the environment around the tumour for some of the patients. Following studies will bring us to the point in time where treatment choices can be made according to tumour characteristics, so we can maximize the number of patients that can be cured from this disease. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9006485
- author
- Josefsson, Hanna LU
- supervisor
-
- Sara Ek LU
- organization
- course
- KIMM05 20192
- year
- 2020
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9006485
- date added to LUP
- 2020-03-19 08:51:34
- date last changed
- 2020-03-19 08:51:34
@misc{9006485,
abstract = {{The tumour microenvironment in Mantle Cell Lymphoma (MCL) is underexplored. Through advancing understanding, it would be possible to stratify patients to the optimal immunotherapy. To enable analysis of more complex phenotypes, compared to single immunohistochemistry (IHC) staining, the aim of this thesis was to evaluate the novel overlay-analysis tool in HALO® using diagnostic MCL. This novel module enabled multiplex analysis and detection of colocalized immune cells, by overlaying images of individually stained IHC slides. The present study was restricted to CD3+ T lymphocytes, and the analysis of CD4, CD8, CD25, FoxP3, T-bet, GATA3, PD-1 and PD-L1 expression. Major technical limitations were identified associated with the overlay functionality in HALO®, and only part of the cohort could be used to draw conclusions related to biology. However, we could determine the frequency of sub-populations of T cells and show that, when the T cell associated markers (CD3, CD4 and CD8) are expressed in close proximity to FoxP3 or PD-L1, it pin-points a small subpopulation of high-risk patients.}},
author = {{Josefsson, Hanna}},
language = {{eng}},
note = {{Student Paper}},
title = {{Spatial Multiplex Analysis of Immune Cell Infiltration in Mantle Cell Lymphoma}},
year = {{2020}},
}