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CD4+ T cells drive anti-tumor immunity elicited by in vivo dendritic cell reprogramming

Ballocci, Tommaso (2024) MOBN03 20232
Degree Projects in Molecular Biology
Popular Abstract
Cancer immunotherapy employs the patients' own immune system to eradicate the tumor. The success of immunotherapies largely depends on an immune cell population, called T cells. T cells have the capacity to differentiate between healthy and malignant cells based on mutations that are displayed on the surface of cancer cells. After recognition of the tumor cell, T cells induce killing. However, tumor cells use different strategies to hide from the immune system by downregulating the presentation of mutated proteins or suppressing the function of other immune cells including T cells. Dendritic cells, another immune cell population, work as sentinels in our body and are required to identify tumor cells and present their mutated proteins to T... (More)
Cancer immunotherapy employs the patients' own immune system to eradicate the tumor. The success of immunotherapies largely depends on an immune cell population, called T cells. T cells have the capacity to differentiate between healthy and malignant cells based on mutations that are displayed on the surface of cancer cells. After recognition of the tumor cell, T cells induce killing. However, tumor cells use different strategies to hide from the immune system by downregulating the presentation of mutated proteins or suppressing the function of other immune cells including T cells. Dendritic cells, another immune cell population, work as sentinels in our body and are required to identify tumor cells and present their mutated proteins to T cells for potent activation against the tumor. The subclass of dendritic cells, referred to as dendritic cells type 1, has been described as crucial to activate potent T cell responses against the tumor and the presence of these cells within tumors of patients has been associated with better survival. However, there is currently no method to generate dendritic cells type 1 for cancer immunotherapy.

Cell reprogramming allows the conversion of one cell type into another for therapeutic purposes. Reprogramming of cells can be performed in tissues to generate the required cell type directly at the location of the disease. Our group has identified factors that allow the reprogramming of tumor cells into dendritic cells type 1 that can activate T cells against tumor cells by presentation of their own mutated proteins. This has been successfully done on cultures of tumor cells within plates. In this study, we hypothesize that the same factors can reprogram cancer cells within tumor tissue in mice to dendritic cells type 1 that will activate T cells and lead to tumor killing and longer survival of mice. We show that reprogrammed tumor cells become dendritic cells within the tumor and remain for 9 days. Within this time-frame of 9 days, reprogrammed cells recruited a subclass of T cells to the tumor, which resulted in the complete eradication of tumors. Mice that successfully eradicated tumors developed immunity and did not grow again tumors. We identified that reprogrammed cells used several mechanisms to activate immune responses against the tumor. After complete eradication of the tumor, one of ten mice developed a tumor at later stages which showed resistance to the immunity established by reprogrammed tumor cells. Reprogramming of this resistant tumor model successfully converted the tumor cells into dendritic cells and led to longer survival of mice, however, the mice could not eradicate tumors completely. Ultimately, this study demonstrates that tumor cells can be reprogrammed into dendritic cells that remain in the tumor for 9 days and activate T cell responses against tumor cells leading to long-term survival of mice. This study paves the way for the development of a new cancer immunotherapy based on reprogramming of tumor cells into dendritic cells and understanding the resistance mechanisms that can limit the success of this immunotherapy in certain types of cancer. (Less)
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author
Ballocci, Tommaso
supervisor
organization
course
MOBN03 20232
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9176104
date added to LUP
2024-10-04 12:00:28
date last changed
2024-10-04 12:00:28
@misc{9176104,
  author       = {{Ballocci, Tommaso}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{CD4+ T cells drive anti-tumor immunity elicited by in vivo dendritic cell reprogramming}},
  year         = {{2024}},
}