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

A New Way to See Inflammation in the Body

Being able to image inflammation can help doctors diagnose, treat, and predict the outcomes of many diseases. However, there isn’t yet a highly accurate and specific imaging method to detect inflammation. To solve this problem, researchers developed a new technique called CD45-PET imaging. This method provides clear and sensitive pictures of inflammation in different disease models.

One of the key findings is that CD45-PET imaging shows how severe a disease is by producing stronger signals in models of lung and bowel diseases. It works better than the current most-used method, called 18F-fluorodeoxyglucose PET, for detecting inflammation. CD45-PET can also track how inflammation changes over time in specific tissues.

The researchers also created a version of CD45-PET for humans, which successfully detects human immune cells in special mouse models that mimic the human immune system. This new imaging method has great potential to help doctors make better decisions by providing a precise, full-body view of inflammation in patients.

From the text: Fig. 1: 89Zr-CD45 nanobody PET probe clearly visualizes immune-cell-rich organs in vivo.

Salehi Farid, A., Rowley, J.E., Allen, H.H. et al. CD45-PET is a robust, non-invasive tool for imaging inflammation. Nature (2025). https://doi.org/10.1038/s41586-024-08441-6

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

Understanding How Cells Shape the Immune Response to Food

Our gut's immune system has a tough job—it needs to peacefully handle food and helpful microbes while staying ready to fight harmful germs. Special cells called antigen-presenting cells (APCs) help guide this balance. They "show" food particles to certain immune cells called CD4+ T cells, which can then decide to either calm down (becoming pTreg cells) or gear up for action (becoming Th cells).

To learn more about how this works, researchers used a tool called LIPSTIC to find which APCs present food particles during normal, calming conditions and during inflammation. They also looked at how this balance can be thrown off during infections. They found that worm infections (helminths) upset the gut's ability to tolerate food by changing the balance of APCs. Normally, cells like cDC1s and Rorγt+ APCs help keep the peace, but helminths boosted inflammatory APCs, mostly cDC2s, which didn’t respond to food particles. This prevented the immune system from overreacting to food during infection, avoiding unnecessary allergic responses.

Canesso, M. C. C., Castro, T. B. R., Nakandakari-Higa, S., Lockhart, A., Luehr, J., Bortolatto, J., Parsa, R., Esterházy, D., Lyu, M., Liu, T.-T., Murphy, K. M., Sonnenberg, G. F., Reis, B. S., Victora, G. D., & Mucida, D. (2024). Identification of antigen-presenting cell–T cell interactions driving immune responses to food. Science. https://doi.org/10.1126/science.ado5088

Turning Bacteria's Weakness into Strength: A New Way to Fight Antibiotic Resistance

Carbapenems are strong antibiotics used when other medicines don’t work against bacterial infections. But some bacteria have become resistant to them by producing an enzyme called VIM-2, which helps them survive the antibiotics. Unfortunately, there are no medicines yet that can stop this enzyme.

Our research found that bacteria with VIM-2 don’t grow well when zinc, an important mineral, is low—like in human blood or animal infections. We studied their genes and processes to learn how they use zinc and found that blocking certain systems weakens them, making it harder for them to grow.

We also discovered that VIM-2 damages the bacteria’s protective outer layer, which makes them easier to kill with the antibiotic azithromycin. In tests with mice, azithromycin worked well to treat infections caused by these resistant bacteria.

These findings show ways we can target weaknesses in resistant bacteria, giving hope for new treatments against infections that are hard to cure.

From:

Tu, M.M., Carfrae, L.A., Rachwalski, K. et al. Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens. Nat Microbiol 10, 53–65 (2025). https://doi.org/10.1038/s41564-024-01883-8