Radiation can quiet the immune system after cancer treatment — scientists may have found how to switch it back on
Radiation therapy is one of the most powerful tools doctors have against cancer. It aims high-energy beams at a tumour, damages the DNA inside cancer cells, and stops them from growing. For many patients, it works. For others, it does not work as well as doctors hope — and until now, one reason for that was only partly understood.
A new study from researchers at the University of Chicago offers a clear explanation, and a possible way forward. It found that radiation can, in some cases, switch on a process in the bone marrow that produces immune cells which protect the tumour instead of attacking it. When the researchers blocked that process in laboratory mice, the same kind of immune cells changed sides and began to help the immune system find and attack cancer.
The work was published in the journal Cancer Cell, and reported on 30 and 31 October. It is early research. No new treatment is available for patients yet, and the drug tested in the study was experimental. But the finding matters because it points to a specific target — a protein called TET2 — and to a specific moment, within a day of radiation, when the unwanted effect begins.
At a glance
What happened: Researchers at the University of Chicago found that radiation activates a protein called TET2 in immune cells made in the bone marrow, turning them into tumour-protecting suppressor cells; blocking TET2 in mice turned those cells into tumour-attacking activator cells instead.
Why it matters: Radiation is given to 50% to 60% of cancer patients, and a rise in suppressor cells after radiation is linked to shorter survival and a higher risk of cancer spreading. A way to stop that switch could make radiation and immunotherapy work better together.
What happens next: The team is exploring how TET2-blocking drugs might be tested with radiation therapy in patients. That testing has not yet been announced as a trial, and patients should not expect a new treatment from this study in the near future.
Radiation’s double edge
Radiation therapy is used in about half to three-fifths of cancer cases, according to the researchers. Its main job is simple to describe: damage the DNA of cancer cells so they cannot keep dividing. In many cases, it also helps the immune system, because damaged cancer cells can release signals that alert immune cells to the tumour.
But radiation can also have the opposite effect. In some patients, it triggers the growth of a group of immune cells called myeloid-derived suppressor cells, or MDSCs. These cells are made in the bone marrow, the soft tissue inside bones where blood and immune cells are produced. From there, they travel to tumours, where they dampen the body’s defences against cancer. In particular, they block CD8-positive T cells, the immune system’s main tumour-killing cells. The researchers said that, in patients, a rise in MDSCs after radiation is linked to shorter survival and a higher risk of metastasis — the spread of cancer from where it started to other parts of the body.
What the team found in patients
The researchers began with people, not only with laboratory animals. They analysed blood samples collected before and after treatment from 33 patients with stage IV non-small cell lung cancer — cancer that had already spread beyond the lung. The patients were enrolled in a clinical trial at UChicago Medicine, where they received high-dose, precisely targeted radiation together with two immunotherapy drugs, nivolumab and ipilimumab.
Among all the immune cell types the team looked at, MDSCs had the highest levels of TET2. TET2 is an enzyme — a type of protein that drives a chemical change in a cell — and in this case it removes chemical tags called methyl groups from genetic material. After radiation, TET2 levels in MDSCs rose further, most sharply in patients whose cancer did not respond to treatment.
“We noticed in a couple of clinical trials that patients who had elevated TET2 following radiation did worse,” said senior author Ralph Weichselbaum, a professor and chair of radiation and cellular oncology at the University of Chicago.
That pattern fitted with earlier reports of better responses to immunotherapy in patients who had TET2 mutations — changes in a gene — in their blood cells, where TET2 did not work in the usual way. Taken together, the two observations pointed in the same direction: TET2 may act as a barrier to effective treatment.
The patient group was small — 33 people, all with the same type of advanced lung cancer, and all in one trial. A small group can reveal a strong pattern, but it cannot prove that the same pattern will hold for every cancer, every patient, or every form of radiation. The researchers therefore tested the idea directly in mice, where they could switch TET2 off in a controlled way and watch what happened.
The switch inside the bone marrow
In the mouse experiments, the researchers deleted the TET2 gene only in myeloid cells, the family that includes MDSCs. They studied three types of cancer in mice — colon cancer, melanoma, and lung cancer — and in each case the mice without TET2 in their myeloid cells did better after radiation: their tumours grew more slowly, they lived longer, and they had fewer, smaller lung metastases.
The team then traced how radiation turns TET2 on. They found that radiation activates a protein called p53, which senses damage inside a cell. In turn, p53 switches on TET2. This happens in the bone marrow within a day of radiation, before the reprogrammed cells travel to the tumour. That timing is important: the unwanted effect does not start in the tumour itself, but early, in the place where the immune cells are made.
The study also looked at the chemical detail of what TET2 does once it is switched on. TET2 is best known for removing methyl groups from DNA. But earlier work by co-senior author Chuan He, a professor of chemistry and of biochemistry and molecular biology at the University of Chicago, had shown that TET2 also acts on RNA, the molecule that carries instructions from DNA to the rest of the cell.
In the new study, TET2 removed a mark called 5-methylcytosine, shortened to m5C, from a group of RNAs known as chromatin-associated RNAs. Chromatin is the tightly packaged form of DNA inside the nucleus, the control centre of the cell. When those RNA marks were lost, the chromatin packed more tightly, silencing genes for type I interferon, a signal that alerts the immune system to threats such as cancer.
He said it was gratifying to see that the same RNA pathway behind TET2’s earlier-known role also accounted for this immune effect. In plain terms, TET2 removed a small chemical mark, the DNA packaging tightened, and the immune system’s alarm signal went quiet.
From suppressors to activators
The most striking part of the study came when the researchers looked at what happened without TET2. When TET2 was absent, the m5C marks on the chromatin-associated RNAs stayed in place. Those marks attracted a protein called MBD6, which helps open chromatin and keep the interferon pathway active.
The myeloid cells then developed into a previously undescribed cell type, named myeloid-derived activating cells, or MDACs. The name is deliberately close to MDSCs, because the two cell types come from the same family. Their jobs, however, are opposite. Unlike MDSCs, MDACs present pieces of tumour proteins to CD8-positive T cells and prime them to attack cancer — like showing the immune system a photograph of its target.
When the researchers transferred MDACs into mice with tumours, tumour growth slowed. A genetic signature of MDACs was also linked to better survival in patients across multiple cancer types, which the reports did not list. In short, radiation resistance here is not a fixed property of a tumour: it is a programme that immune cells can be switched into, and, at least in mice, switched out of.
Testing a blocker in mice
Deleting a gene in mice is a powerful way to test an idea, but it is not a treatment, so the team took the next step and tested an experimental drug that blocks TET2. When that drug was combined with radiation, the researchers observed slower tumour growth, a reduced number and size of lung metastases, and an improved response to immunotherapy.
“If you block TET2, you change these immunosuppressive myeloid cells into an immunostimulant, antigen-presenting myeloid compartment that enhances immunotherapy and radiotherapy responses in mice and markedly decreases distant metastasis,” Weichselbaum said.
The words “in mice” matter here: a drug that works in mice does not always work in people, and an experimental drug may have side effects that only appear when it is given to people, or together with radiation and immunotherapy. The reports did not name the experimental drug or give its dose, so this article does not give those details either. What the reports do say is that the team is now exploring how TET2 inhibitors — drugs that block TET2 — might be tested with radiation therapy in patients. That is the next step, not a finished treatment. A test in patients would need to answer questions the mouse work cannot: is the drug safe in people, does it change MDSCs into MDACs in people in the same way, and does it actually improve survival?
What the finding could change
If the result holds in people, it could change how doctors think about combining radiation and immunotherapy. The two treatments are often used together because, in theory, they should help each other: radiation damages the tumour and releases signals, and immunotherapy helps T cells act on those signals. In practice, the combination works well for some patients and poorly for others. The new study offers one reason why: if radiation also raises TET2 and produces MDSCs, then the treatment itself is, in some patients, creating part of the resistance it is trying to overcome. Blocking TET2 at the right time could remove that obstacle.
The researchers also pointed to a second possible target: the chromatin-associated RNAs that control this switch could themselves serve as drug targets. “It points the way toward not only targeting TET2, but targeting these chromatin-associated RNAs,” Weichselbaum said. “I think it’s a way maybe to prevent or treat metastasis.” The word “maybe” should be kept: a treatment that reduced metastasis in mice is a real lead, not yet a treatment that reduces metastasis in people.
What this does not mean yet
It is worth being clear about what has not changed. Radiation therapy remains a standard, effective treatment for many cancers. This study does not suggest that patients should delay or refuse radiation, and it does not suggest that TET2-blocking drugs are available, safe, or suitable for any patient today. The human evidence is a pattern in 33 patients with one type of advanced lung cancer, and the evidence that blocking TET2 changes the outcome comes from mice with three types of cancer. Both parts are valuable, and both have limits.
For patients and families, the practical message is therefore a cautious one. If you are receiving radiation, or are due to receive it, talk to your own cancer team. Do not seek out an experimental TET2 drug, and do not change your treatment on the basis of a laboratory study. Clinical trials are the safe, controlled way to find out whether a new idea helps people, and whether it is safe. The study was supported by the National Institutes of Health, the Chicago Tumor Institute, and the Lung Cancer Research Foundation.
Frequently asked questions
What is TET2?
TET2 is a protein, also called an enzyme, that removes chemical tags called methyl groups from DNA and RNA. In the new study, radiation switched TET2 on in immune cells made in the bone marrow, helping turn those cells into suppressor cells that protect tumours. Blocking TET2 in mice had the opposite effect.
What are MDSCs and MDACs?
MDSCs are myeloid-derived suppressor cells. They are made in the bone marrow, travel to tumours, and block the immune system’s main tumour-killing cells, the CD8-positive T cells. MDACs are myeloid-derived activating cells, a cell type described for the first time in this study. Unlike MDSCs, MDACs present pieces of tumour proteins to CD8-positive T cells and prime them to attack cancer.
Does this mean radiation therapy is harmful?
No. Radiation therapy is a standard treatment that helps many patients, and it is given to 50% to 60% of cancer patients. The study found that in some cases radiation can also trigger a process that protects the tumour. That is a side effect of the treatment’s effect on the immune system, not a reason to refuse radiation.
Is there a new TET2 drug patients can take now?
No. The team tested an experimental TET2-blocking drug in mice, and the reports did not name the drug. The team is exploring how TET2 inhibitors might be tested with radiation therapy in patients. No patient trial was announced in the reports used for this article.
How many patients were studied?
The human part of the study analysed blood samples from 33 patients with stage IV non-small cell lung cancer, in a clinical trial at UChicago Medicine. They received high-dose, precisely targeted radiation with the immunotherapy drugs nivolumab and ipilimumab. That is a small, specific group, so the findings need testing in larger groups.
Could this help cancers other than lung cancer?
Possibly, but that is not yet known. In mice, the benefit of deleting TET2 in myeloid cells was seen in models of colon cancer, melanoma, and lung cancer. A genetic signature of the new MDAC cells was also linked to better survival in patients across multiple cancer types, which the reports did not list.
Conclusion
Cancer treatment is often described as a fight against the tumour. This study is a reminder that the immune system is part of that fight, and that treatment itself can change which side the immune system is on.
Radiation can damage cancer cells and alert the immune system. It can also, through p53 and TET2, switch off the immune alarm and produce cells that shield the tumour. The University of Chicago team found that switch, traced it to the bone marrow within a day of radiation, and showed that blocking it in mice turned protector cells into attacker cells.
That is a clear, testable idea. It is not yet a treatment. The next step is to find out whether a TET2-blocking drug is safe in people, whether it changes human immune cells in the same way, and whether it improves survival with radiation and immunotherapy. Until those questions are answered in clinical trials, the finding should be read as what it is: a promising lead, explained in unusual detail, on how to make one of cancer’s oldest treatments work better.
Sources
- https://medicalxpress.com/news/2026-10-reversing-immune-suppression-cancer.html (MedicalXpress, 31 October 2026)
- https://www.news-medical.net/news/20261030/Targeting-specific-enzyme-reverses-radiation-induced-immune-suppression-in-cancer.aspx (News-Medical, 30 October 2026)
- https://www.newswise.com/articles/reversing-radiation-activated-immune-suppression-in-cancer/?ad2f=1&aid=857640 (Newswise, 29 October 2026)
- https://www.cell.com/cancer-cell/abstract/S1535-6108(26)00394-6 (Cancer Cell, 2026)
This article is for general information and education only. It is not legal or financial advice.
