Cancer is often described as a master of survival, employing countless strategies to outwit the body’s defense mechanisms. One of the immune system’s key soldiers against tumors are tumour-infiltrating lymphocytes (TILs)—immune cells that penetrate the tumor’s microenvironment to attack cancer cells directly. However, recent research has revealed a surprising way that cancer cells can neutralize these immune warriors: by transferring defective mitochondria into TILs.

The Role of Mitochondria

Mitochondria are often called the “powerhouses” of the cell because they generate the energy cells need to function, grow, and divide. Proper mitochondrial function is essential for all cells—including T cells involved in the immune response. When mitochondria are compromised, the cell’s energy production falters, leading to dysfunction and sometimes cell death.

A Surprising Discovery

In studies involving samples from three individuals with cancer, scientists identified that the mitochondria found in TILs shared the same genetic mutations as those in the tumor cells. This was the first clue that something unusual was happening. How could immune cells, genetically distinct from cancer cells, end up with the exact same mitochondrial mutations?

Researchers then set up a laboratory experiment, growing cancer cells alongside TILs. They tagged the cancer cells’ mitochondria with a fluorescent marker to track exactly where these mutated organelles went. Remarkably, after just 24 hours, some of the TILs began to carry this fluorescent “label,” indicating that they had taken on faulty mitochondria from the tumor cells. By 15 days, the TILs’ original, healthy mitochondria were almost completely replaced by defective versions from the cancer cells.

How Defective Mitochondria Weaken Immune Cells

Once TILs acquire dysfunctional mitochondria, their behavior changes dramatically:

1. Reduced Ability to Divide: T cells rely on rapid cell division to expand their numbers and mount an effective immune response. Mutated mitochondria disrupt this energy-intensive process, slowing down or halting TIL proliferation.
2. Increased Cell ‘Suicide’: Cells have a natural self-destruct program called apoptosis. When energy production is compromised—and signals of cellular stress mount—cells are more inclined to undergo programmed cell death. TILs loaded with defective mitochondria were more prone to this fate.
3. Impaired Function: Beyond dividing, effective T cells must communicate with other immune cells and release molecules that target cancer. Suboptimal energy production hampers all these functions, leaving TILs less capable of delivering a lethal blow to tumor cells.

Why This Matters

This newly uncovered tactic highlights the complexity of the tumor microenvironment. Cancer cells don’t just passively avoid the immune system; they can actively compromise it from within. By transferring defective mitochondria, tumors effectively sap the energy resources T cells depend on, blunting the immune response.

For oncologists and researchers, these findings open new avenues for therapeutic intervention. If scientists can block or reverse the transfer of defective mitochondria—or restore T cells’ healthy mitochondrial function—then TILs might retain their vigor and improve their cancer-killing potential. This could bolster existing treatments such as CAR T-cell therapy or checkpoint inhibitors, which rely on the robust function of T cells.

Looking Ahead

Understanding how cancer cells sabotage the immune system underscores a broader truth: tumors are not isolated masses but integrated players in a dynamic ecosystem. By employing strategies that corrupt immune defenses, they improve their chances of survival. Future research aims to clarify precisely how cancer cells orchestrate mitochondrial transfer, and whether this process is common across many cancer types.

If scientists can inhibit or prevent the uptake of defective mitochondria by TILs, it could lead to more effective immunotherapy strategies. Ultimately, unraveling this devious trick might offer a pathway to empower the body’s own defenders—paving the way for more successful, long-lasting treatments for cancer.