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Emmanuel Donnadieu and INSERM colleagues publish their work on T cell migration in Nature Communications

May 14, 2024

Emmanuel Donnadieu and INSERM colleagues publish their work on T cell migration in Nature Communications

May 14, 2024
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NexTGen researcher Dr. Emmanuel Donnadieu and his team from INSERM published a paper in March 2024 in the journal Nature Communications titled “Mitochondrial metabolism sustains CD8+ T cell migration for an efficient infiltration into solid tumors.”  

 

Patient response to immunotherapy is dependent, among other things, on the ability of CD8+T cells (killer T cells) to infiltrate solid tumors and attack malignant cells. Solid tumors have complicated structures and hostile microenvironments, making it difficult for CD8+T cells to migrate to the tumor carry out their killer function. Similarly, this limits the effectiveness of CD8+CAR T cells during immunotherapy treatment. 

 

The investigation detailed in this paper lead the INSERM team to identify the methods by which CD8+T cells harness the energy that is required to move through the microenvironment and penetrate tumors. The team shows that the way the mitochondria process the nutrients glucose and glutamine to produce ATP and ROS gives the T cells the energy they need. This process is called the tricarboxylic acid (TCA) cycle

 

This research has clinical implications for the CAR T cell therapy that NexTGen is working on. If scientists can develop a drug strategy to target the mitochondria to improve its activity, then CD8+T cell migration and tumor penetration activity will in-turn become enhanced. This would allow for enriched efficacy of CD8+CAR T cells in treating solid tumors. 

 

Key terms 

CD8+T cells: Also known as cytotoxic T cells or killer T cells. Part of the immune system, a type of white blood cell responsible for recognizing and destroying cancer cells and cells infected with pathogens. 

Microenvironment: The normal cells, immune cells, molecules, and blood vessels that surround and feed a tumor. 

Mitochondria: Small structures inside cells that generate energy for the cell by converting nutrients from food into a form of energy that cells can use (ATP). 

ATP (adenosine triphosphate): “Energy currency” of the cell. A molecule that stores and releases energy for cellular function. 

ROS (reactive oxygen species): Small molecules produced as a byproduct of cellular metabolism that play an important role in immune defense and cell signaling. 

TCA cycle: A series of chemical reactions that occur in cells to generate energy from food molecules. It is a key part of cellular respiration, the process by which cells convert nutrients into energy. 

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