Skip to main content

LUP Student Papers

LUND UNIVERSITY LIBRARIES

Identifying epigenetic and mutational barriers limiting cancer cell reprogramming into dendritic cells

Linfeldt, David (2023) MOBN03 20222
Degree Projects in Molecular Biology
Popular Abstract
Cracking the Code: Why Cancer Cells Struggle to Transform into Antigen-Presenting Dendritic Cells

Since cancer is one of the leading causes of death worldwide, the possibility of converting cancer cells into other cell types represents an interesting approach to fighting cancer. Transforming cancer cells into immune cells by reprogramming their cell identity into immune cells could be a smart way to treat cancer. Extensive research has been conducted to find ways to reprogram cancer cells into dendritic cells. Dendritic cells play a critical role in orchestrating both the innate and adaptive immunity and are important in anti-tumor immunity. A breakthrough occurred when it became possible to reprogram cancer cells into immune cells... (More)
Cracking the Code: Why Cancer Cells Struggle to Transform into Antigen-Presenting Dendritic Cells

Since cancer is one of the leading causes of death worldwide, the possibility of converting cancer cells into other cell types represents an interesting approach to fighting cancer. Transforming cancer cells into immune cells by reprogramming their cell identity into immune cells could be a smart way to treat cancer. Extensive research has been conducted to find ways to reprogram cancer cells into dendritic cells. Dendritic cells play a critical role in orchestrating both the innate and adaptive immunity and are important in anti-tumor immunity. A breakthrough occurred when it became possible to reprogram cancer cells into immune cells using three molecules called PU.1, IRF8 and BATF3. When added to cancer cells, they transform into dendritic cells. However, certain cancer cell lines show very low reprograming into dendritic cells. Therefore, my goal was to investigate the factors that hinder the reprogramming of cancer cells into dendritic cells.

The Pereira lab at Lund University was looking for a way to reprogram cells into dendritic cells, as they are crucial for anti-tumor immunity. The solution was found when the group discovered three molecules PU.1, IRF8 and BATF3 that can be introduced into cells and cause them to transform into dendritic cells. It was later discovered that these molecules also have the potential to reprogram cancer cells into dendritic cells. This was an exciting discovery because it has the potential to become a new form of immunotherapy, allowing for increased numbers of dendritic cells that can seek out tumor cells and trigger immune responses at their sites. However, reprogramming of various types of cancer cells from different origins showed significant variations in their efficiencies of reprogramming.

Since certain cancer cell lines exhibited very low reprogramming efficiencies, we aimed to identify the underlying barriers hindering their differentiation into dendritic cells. We evaluated the role of epigenetics as a possible barrier since it is important in maintaining cell identity which could decrease the transformation of cancer cells to dendritic cells. We therefore tested epigenetic modifiers that unwind nucleosomes and remove methylation on the DNA which result in a more open chromatin making the DNA accessible for transcription. Through this experiment, we found that many types of cancer cells improved in their ability to transform into dendritic cells. This suggests that epigenetic barriers partially impede the transformation of cancer cells into dendritic cells.

However, since the cancer cell lines were only partially increased by epigenetic modifiers during reprogramming, other barriers are likely involved. As cancer cells exhibit mutations, we wanted to investigate whether these mutations may be the cause of impaired reprogramming in some cancer cells. To identify the mutations responsible for the impaired reprogramming, we analyzed the mutations frequently present in the poorly reprogrammed cells and eliminated those mutations that were also present in the well-reprogrammed cancer cell lines. In this way, we identified mutations within six genes with various functions that correlated with low reprogramming which could be responsible for impaired reprogramming. In the future, we would like to investigate these mutations and their impact on reprogramming to see if they are mutational barriers in reprogramming cancer cells into the orchestrating dendritic cells.

Masters degree project in Molecular Biology, 60 credits, 2023
Department of Biology, Lund University

Handledare: Olga Zimmermannova
Molecular Medicine and Gene Therapy, BMC A12 (Less)
Please use this url to cite or link to this publication:
author
Linfeldt, David
supervisor
organization
course
MOBN03 20222
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9136024
date added to LUP
2023-09-01 15:09:37
date last changed
2023-09-01 15:09:37
@misc{9136024,
  author       = {{Linfeldt, David}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Identifying epigenetic and mutational barriers limiting cancer cell reprogramming into dendritic cells}},
  year         = {{2023}},
}