How Cancer Outsmarts Your Immune System: The Role of Mitochondrial Hijacking

Imagine your immune system trying to fight off cancer. Normally, your T cells are like soldiers, ready to attack and destroy cancer cells. But cancer cells have sneaky ways to avoid being attacked. They change the environment around them and disrupt the mitochondria—the energy factories—in your immune cells, particularly in tumor-infiltrating lymphocytes (TILs). This makes it harder for your immune system to do its job.

Now picture this: the cancer cells’ mitochondria, which may carry harmful mutations in their DNA, can actually transfer to your T cells. Typically, your T cells can get rid of damaged mitochondria through a process called mitophagy, triggered by harmful byproducts called reactive oxygen species. But cancer mitochondria come equipped with special molecules that prevent this cleanup process. These molecules stick to the cancer mitochondria and hitch a ride into your T cells, replacing your healthy mitochondria.

When your T cells take on these faulty mitochondria, they start to malfunction. They lose energy, stop working properly, and can no longer "remember" how to fight the cancer effectively. This weakens your immune system’s ability to attack the tumor. If your tumor has these mitochondrial DNA mutations, treatments like immune checkpoint inhibitors might not work as well, especially if you have melanoma or non-small-cell lung cancer.

This discovery shows you how cancer can trick your immune system in ways scientists didn’t fully understand before. Knowing this could lead to new, better treatments that help your immune system fight back.

In the study linked below, researchers looked at tissue samples from patients and found that the mitochondria in TILs sometimes carry the same DNA mutations as the cancer cells. The researchers also found that if a patient’s tumor has these mitochondrial DNA mutations, treatments like immune checkpoint inhibitors may not work as well, especially for melanoma or non-small-cell lung cancer.

These findings uncover a new way that cancer tricks the immune system and could help scientists develop better cancer treatments in the future.

From text: Fig. 5: mtDNA-mutated mitochondrial transfer reduces antitumour immunity in vivo.

Ikeda, H., Kawase, K., Nishi, T. et al. Immune evasion through mitochondrial transfer in the tumour microenvironment. Nature (2025). https://doi.org/10.1038/s41586-024-08439-0

Improving the Immune System’s Ability to Fight Cancer

The immune system uses a molecule called interleukin-10 (IL-10) to help control inflammation and avoid excessive damage to the body. However, tumors often increase IL-10 levels to suppress the immune system, which helps them grow and spread. Recent studies show that IL-10 production depends on signals from mitochondria, the parts of cells that produce energy.

We discovered that a substance called S3QEL 1.2, which blocks certain chemicals (reactive oxygen species or ROS) from being made in mitochondria, reduces IL-10 levels in immune cells called macrophages. Another substance, myxothiazol, also lowers IL-10 by targeting the same part of the mitochondria. This happens because these substances suppress a protein called c-Fos, which is needed for IL-10 production.

When tested in mice, S3QEL 1.2 lowered IL-10 levels and helped their immune systems fight tumors more effectively, slowing the growth of melanoma. This research shows that blocking specific mitochondrial signals may help improve the immune system’s ability to fight cancer.

From the text: Fig. 2. Complex III inhibition reveals a specific transcriptional signature in activated macrophages

Zotta, A., et al. (2025). Mitochondrial respiratory complex III sustains IL-10 production in activated macrophages and promotes tumor-mediated immune evasion. Science Advances, 11(4), eadq7307. https://doi.org/10.1126/sciadv.adq7307

Turmeric and cancer

Cancer can be a really difficult disease to fight using conventional methods. The cells in your body are in a state of flux. They are constantly dieing-off (senescence) and being replaced with new cells. The body needs to replace with new cells though only those that have been lost through cell death. Sometimes though that is not what happens.

Cancer cells are cells that have a faulty mechanism for turning themselves off. Both the replacement of healthy cells that have specific functions with cancer cells that do not perform those functions and the physical presence of the cancer mass have an impact on the body's functions such that death can occur if the cancerous mass is not removed either through surgery (not all cancers can be removed physically) or with chemical (chemo) therapy and/or radiation. Often a combination of these approaches are used.

Unfortunately not all cancers can be fought off in this way. Some are resistant (have faulty apoptotic pathways) and can even lead to increased malignancy with treatment over time. This tendency can either be inherent in the cancer type (shows no response to chemo/radiation therapy) or be acquired over time (initial response that is later lost.) But recent work on shows there may be some hope for future treatments on these resistant cancers.

There is a process of cell death termed mitotic catastrophe which in mammalian cells is caused by aberrant mitosis. This is sciencese for death of cells by dividing into various other (non-viable) forms. A mitotic catastrophe causes massive die-off of the affected cells. This process is generally prevented from occuring in cells due to a body chemical given the name of survivin (how creative! I guess that's better than zercoxinol or something like that.). It turns out survivn is found in all growing cell locations but not in mature tissue. Here is where things get interesting...

Turns out there is a way to interfere with survivin (remember servivin helps keep cancer cells alive by preventing mitotic catastrophe) and it is derived from turmeric.

From wikipedia:

Turmeric (Curcuma longa, also called tumeric or kunyit in some Asian countries) is a spice commonly used in curries and other South Asian cuisine.

An active ingredient in turmeric is a compound called curcumin. In a recent article in the journal International Journal of Cancer (Volume 119, Issue 8, Pages 1811-1818 23 May 2006) titled Resistance to apoptosis of HCW-2 cells can be overcome by curcumin- or vincristine-induced mitotic catastrophe Magalska et al state:

It has been very recently shown that curcumin (diferuloylmethane), a natural dye from the rhizome of Curcuma longa [turmeric] and a known apoptotic inducer, downregulates survivin. In other experiments, it has been shown that curcumin arrests MCF-7 cells in G2/M, disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer,[9] displaying cell morphology that fits very well to the mitotic catastrophe picture.

Well there is a lot of sciencese but the short of it is that this compound in turmeric may well play a future role in cancer suppression. This of course does not mean that you should expect that eating this turmeric will prevent cancer or help you if you have it. The body is far too complex a system to jump to that conclusion.

I will write more later about turmeric and a role it might have in helping older people keep mental acuity.

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