Researchers have revealed a new finding that could improve cancer care immunotherapy treatments, particularly for chronic lymphocytic leukaemia (CLL) and other cancers
The new study, published in Cellular & Molecular Immunology, explores how cancer cells impact the energy metabolism of immune cells, revealing a key obstacle to successful treatment.
By understanding this challenge, scientists are one step closer to enhancing the effectiveness of immunotherapies like CAR-T cell therapy, offering hope for better outcomes in the fight against cancer.
Enhancing the efficiency of immunotherapies
CLL, a type of cancer that affects white blood cells, is the most common form of leukaemia in the Western world, primarily impacting older adults.
Although there have been advancements in treatment options, CLL is still incurable and usually requires expensive therapies that are not always effective.
For patients with certain types of cancer, like acute B-cell leukaemia, CAR-T cell therapy, where a patient’s T cells are redirected to target and destroy cancer cells, has proven to be a potentially life-saving option.
However, this therapy works for only a small percentage of CLL patients and comes with a hefty price tag, often exceeding $250,000 per patient.
While immunotherapy treatments have shown promise in some cancers, many still struggle to effectively activate the body’s immune system.
In CLL, for example, immune cells called T cells often fail to eradicate tumours. The new research provides critical insights into why this occurs, pointing to a problem in the energy management of T cells.
Recharging T cells: A new pathway for improved immunotherapy
Healthy T cells rely on energy to function effectively. After recognising a target, these cells increase their absorption of cholesterol and fats, which fuels their ability to proliferate and attack cancer cells. However, this process fails to occur when T cells come into contact with CLL cells. The T cells do not absorb enough fuel, preventing them from growing and attacking the cancer.
Researchers also discovered that the mitochondria, the powerhouses of cells, do not function properly in CLL patients.
In these cases, the mitochondria become damaged, disrupting the energy supply needed for T cells to effectively target and destroy cancer cells.
This discovery adds a new layer to understanding how cancer cells interact with the immune system and highlights a critical area for improvement in immunotherapy treatments.
To address this issue, the research team tested ways to “recharge” the energy supply of T cells. They found that using an existing drug that affects energy management significantly improved the performance of CAR-T cell therapy in the laboratory.
This could pave the way for more effective CAR-T cell treatments in the future, offering new hope for patients whose immune cells struggle to overcome cancer’s disruptive effects.
Looking ahead, the researchers are exploring ways to genetically modify T cells to make them more resilient to the energy disruptions caused by cancers like CLL.
Ensuring that the cells’ fuel supply and mitochondria remain functional could help enhance the effectiveness of immunotherapy in many types of cancer. If successful, these approaches could be applied to cancers beyond CLL, offering a more universal solution for improving the body’s immune response.
Combination therapies
The researchers are also investigating combination therapies in clinical trials that could further enhance treatment outcomes.
One promising study, the HOVON study, is testing a drug that both weakens leukaemia cells and enhances the ability of T cells to target and attack these cancer cells.
Early results show that combining such therapies could significantly improve the effectiveness of immunotherapy treatments.
