Study learns how cancer cells highjack the immune system

T cells play a crucial role in the body’s fight against cancer, acting as the immune system’s frontline defenders.

However, scientists are still uncovering the many ways in which cancer weakens these vital cells, and limits their ability to attack malignant growths.

In a new study, researchers from Amsterdam UMC and Moffitt Cancer Center have explored how leukemia disrupts the “energy management” of a patient’s T cells.

Their findings provide fresh insights into why immune responses falter, and open the door to potential breakthroughs in cancer treatment.

Understanding T cells – the basics

T cells are like the body’s personal security team, constantly on the lookout for invaders like viruses, bacteria, and even cancer cells.

These immune system warriors come from the bone marrow but mature in the thymus (hence the “T” in their name).

Once they’re fully trained, they patrol the bloodstream, ready to recognize and attack anything that doesn’t belong.

Some T cells act like detectives, identifying threats, while others go full attack mode, destroying infected cells before the problem spreads.

T cells don’t just fight infections also help the immune system remember past enemies. That’s why vaccines work – they train T cells to recognize specific threats so the body can respond faster next time.

Energy crisis in T cells

In their study, the researchers examined chronic lymphocytic leukemia (CLL) – the most prevalent form of leukemia in the Western world. They discovered that contact with CLL cells leads to a severe energy crisis in T cells.

Their findings not only shed light on the persistent challenge of treating this disease, particularly in elderly patients, but also potentially open up new avenues for the development of more effective treatments.

Unique to their research was the focus on T cell energy management, an aspect that is often overshadowed by the race to improve cancer cell identification by our immune system.

T cells are critical elements in the body’s internal defense mechanism and understanding how and why they falter is vital to improving cancer therapies.

Fueling the fight against cancer

The research team discovered that healthy T cells dramatically increase their cholesterol and fat absorption immediately after identifying their targets.

The fuel derived from this process enables these cells to multiply and maintain their offensive against cancer proliferation.

However, they lose this crucial ability when they come into close proximity with leukemia cells, thus undermining their effectiveness.

This critical finding supports the results of a parallel study that was conducted by the same team. It was shown that in CLL patients, the mitochondria – providers of energy for cellular functions – operate sub-optimally.

The impairment of the mitochondria reduces the ability of T cells to attack cancer cells effectively.

Recharging T cells for greater effectiveness

The researchers succeeded in re-energizing T cells in a promising attempt to enhance their operational efficiency.

By utilizing an existing drug that affects energy management, they were able to significantly improve the effectiveness of CAR T-cell therapy, a treatment involving the redirection of a patient’s own T cells against cancer cells.

“We hope this discovery will lead to improved success of CAR T-cell treatment in the future,” shared Javier Pinilla-Ibarz M.D., Ph.D, the Senior member at Moffitt Cancer Center.

“This discovery brings us one step closer to making CAR T-cell treatment more successful for a greater number of patients.”

More importantly, it opens the door for exploring similar strategies in other cancers where immune cells struggle to sustain their attack.

By addressing the energy crisis in T cells, the team hopes to enhance immunotherapy across a wider range of cancers.

New horizons in cancer treatment

The researchers are ambitiously developing solutions to outsmart the disruptive effects of CLL on T cell energy management.

The objective is to modify specific genes, thus making these immune cells more resistant and ensuring the continuous functionality of their fuel supply and “engine.”

And the scope of this research extends far beyond CLL; if successful, the approach could be applied to the treatment of other cancers, expanding the reach and effectiveness of immunotherapy.

Why does any of this matter?

An international clinical trial has already shown promising results, revitalizing hope for more effective treatments.

It demonstrated that combining a drug that reduces leukemia cell count, with a procedure that attracts T cells to cancer cells significantly increases the effectiveness of treatment.

This approach essentially tackles the cancer cells first, ensuring the body’s immune functioning isn’t initially compromised by the disease.

It presents the potential for combination therapies that can be much more effective in battling various types of cancers.

Arnon Kater, professor of Translational Hematology at Amsterdam UMC, concluded that cancer’s impact on immune cell metabolism disrupts the efficient energy supply that is critical for immune function.

These findings, therefore, have the potential to enhance existing treatments significantly, and bring us one step closer to winning the battle against cancer.

The full study was published in Blood Journal.

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