Healing the gut after cancer therapy: Immune cells turn damage into repair

Regulatory T cells (Treg cells), a specialized type of immune cell, are usually seen as “peacekeepers” that prevent excessive immune attacks. Surprisingly, a new study published in Signal Transduction and Targeted Therapy shows that Treg cells utilize inflammatory signals to start repair processes following cancer therapy.

The research conducted by the LIT Cooperation Group Innate Immune Sensing in Cancer and Transplantation in cooperation with researchers from the Department of Radiation Oncology at the Technical University of Munich (TUM) uncovers how the body’s own immune system can be harnessed to repair the intestinal lining and improve survival.

Until now, inflammation in the intestine was primarily considered harmful. “Now we have seen that under certain conditions the immune system uses inflammatory signals to start healing,” says Prof. Hendrik Poeck, managing senior physician at the Clinic and Polyclinic for Internal Medicine III.

“These findings could have important clinical implications for many patients undergoing cancer treatments that harm the intestine,” says Dr. Julius Fischer, first and corresponding author of the study, research group leader, and specialist in radiation oncology at TUM University Hospital.

IFNγ and IL-10 have combined effects on the gut’s natural repair units

Ph.D. student and first author of the study, Sascha Göttert, from the Clinic and Polyclinic for Internal Medicine III at UKR, discovered that in both mouse models and patient samples, Treg cells produce two inflammation-associated molecules that work together to stimulate intestinal stem cells.

“We found that interferon-gamma (IFNγ) and interleukin-10 (IL-10) act in concert to influence the gut’s natural repair units,” explains Göttert.

While IFNγ alone triggers rapid cell growth but exhausts the intestinal stem cell pool, and IL-10 alone provides only weak support, their combination delivers a powerful yet sustainable repair signal. This cooperation supports both rapid healing and long-term regeneration of the gut following immune- and radiation-related injuries, such as after stem cell transplantation or abdominal irradiation.

Study underscores the central role of intestinal stem cells and Treg cells as ‘master repairers’

Patients receiving intensive cancer treatments—such as radiation or stem cell transplantation—often suffer from severe damage to the intestinal lining.

“This not only causes painful inflammation and infectious complications but also worsens long-term clinical outcomes,” says Dr. Julius Fischer. Following the results, the immune system’s own repair program seems to play an important role in protecting the gut during cancer therapy.

“This study highlights the interplay of intestinal stem cells and Treg cells that release immune signaling molecules as master repairers for injured tissues,” Prof. Hendrik Poeck, Head of the LIT Cooperation Group Innate Immune Sensing in Cancer and Transplantation states.

Uncovering these processes has the potential to enable new therapeutic strategies to promote intestinal repair.

Tissue-healing therapies could transform cancer outcomes

Recently, a Nature Communications study by Poeck’s team showed that intestinal bacteria or a specific metabolite can also strengthen intestinal stem cells to prevent tissue injury following transplantation. Both studies seen in combination mean important translational progress in the treatment of severe side effects of cancer and transplant therapies—on the one hand, through the targeted use of engineered immune cells that produce certain immune molecules, and on the other hand, through microbiota-derived preparations or nutritional strategies.

Led by researchers from the UKR and LIT, both approaches are advancing toward early clinical trials within the National Center for Tumor Diseases (NCT) network, targeting patients undergoing transplantation or CAR T-cell therapy for blood cancers.