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Disease and treatment

Antibiotics inhibit lymphoma of the skin

People with cutaneous T-cell lymphoma (CTCL) often also get bacterial skin infections. While attempting to learn how to counteract infection caused by staphylococci in a person with CTCL, researchers noticed that antibiotics also suppressed the cancer symptoms. A new study on a larger group of people with CTCL showed that antibiotics actually inhibit both infection and cancer. Researchers hope that this method can also inhibit other types of cancer.

When people develop cancer, the cancer cells and the body’s other cells begin to battle over resources. The outcome of this conflict is crucial. If the cancer cells receive the necessary nutrition, they grow and divide and the cancer spreads. Researchers are therefore constantly trying to find new methods to starve cancer cells without harming the body’s other cells. One surprising method of achieving this arose unexpectedly.

“When people develop CTCL, the immune system’s T cells develop abnormally and attack the skin. People with CTCL are often also plagued by bacterial skin infections. We attempted to counteract these bacteria with antibiotics and discovered that they also inhibited the cancer. We now know the reason: the toxins the bacteria produce stimulate the growth of the cancer cells. By removing the bacteria, we remove the extra fuel the bacterial infection pours on the cancer fire,” says Niels Ødum, Professor, LEO Foundation Skin Immunology Research Center, University of Copenhagen.

Bacteria boost the growth of cancer cells

CTCL is a rare type of non-Hodgkin lymphoma that affects the skin. In the vast majority of people with non-Hodgkin lymphoma, it affects the B cells (memory cells) of the immune system. However, among people with the less common CTCL, it affects the T cells. These cells contain the immune system’s key defence system, tasked with finding cells in the body that have been infected by either viruses or bacteria.

“In the past, doctors were very reluctant to prescribe antibiotics to people with skin infections because they feared that antibiotic-resistant bacteria would develop. Our new research changes that view. We got the idea from laboratory tests showing that the toxins the bacteria produce can boost cancer cell growth in test tubes.”

Lars Iversen, Clinical Professor, Department of Dermatology and Venereology, Aarhus University had also noticed that prescribing antibiotics for blood poisoning noticeably improved the skin of a person with CTCL. The researchers’ idea, therefore, was to give people a very powerful antibiotic regimen that could effectively combat staphylococcal infection to prevent it from recurring. The researchers also investigated how this affected the cancer cells.

“We were positively surprised to discover that the staphylococci in the skin secrete toxins that cause immune cells to release cytokines, which are important signalling substances that give the cancer cells an extra boost, enabling them to grow and divide more easily. By eliminating the staphylococci, we removed that boost so the cancer cells lost their growth advantage over the body’s other cells. This treatment was like removing a lot of fuel from the fire.”

The new antibiotic treatment has only been tested on eight people, but it reduced the fraction of malignant T cells considerably among six of these people. All participants experienced a marked decrease in clinical symptoms in response to this aggressive, short-term treatment with antibiotics.

“Because of the fear of antimicrobial resistance, we were excited to see whether the effect would last, but we still found improvements for up to 6 months after the treatment ended. Antibiotic treatment therefore appears to break a vicious circle and slow the increasingly rapid growth of cancer cells.”

Alternative to current cancer treatment

The new results are pioneering in many ways. Antibiotics have previously been reported to improve the symptoms of some individuals, but researchers had never previously investigated how antibiotics affect cancer.

“The results are groundbreaking because this is the first time that bacteria and CTCL have been directly linked. The research is the result of many years of work combining molecular and genetic studies in laboratory experiments with clinical studies of carefully selected people.”

However, there is a way to go between pilot experiments involving eight people and achieving a standard treatment. Before this can happen, major clinical trials need to be carried out to determine the people and the disease stages that are optimal for this treatment. Nevertheless, the researchers are so positive that they are already investigating whether the treatment can be used in other contexts.

“We think that the same type of treatment could inhibit other types of skin cancer. We are now investigating how to reinforce the current cancer treatment with antibiotics and to find new ways to attack the bacteria without using antibiotics. In other words, finding new agents that can remove the growth benefits that bacteria give the cancer cells in their struggle against the body’s immune system – without risking the development of antimicrobial resistance.”

Antibiotics inhibit tumor and disease activity in cutaneous T cell lymphoma” has been published in Blood (Journal of the American Society of Hematology). The study is a collaboration between the LEO Foundation Skin Immunology Research Center, University of Copenhagen; Aarhus University and Aarhus University HospitalZealand University Hospital and collaborators in the United States and Germany. The study received support from the LEO Foundation, the Novo Nordisk Foundation (Tandem Programme grant), Independent Research Fund Denmark, the Lundbeck Foundation, the Danish Cancer Society and TV2’s Beat Cancer Fundraiser.

Niels Ødum
Professor
Our goal is to find novel disease mechanisms and molecular targets, that can be used for innovative therapies for inflammatory skin diseases and cutaneous T cell lymphoma. The group works to unravel the interplay between immune, skin cells, and the microbiota to understand, what drives disease progression and resistance to treatment. As inflammation damages the skin barrier, it paves the way for microbial colonization, that fuels more inflammation and disease progression. “Severe skin inflammation and lymphoma arise in the crossfire between skin, immunity, and infection. To find new ways to break the vicious circle, we therefore have to attack and correct all three players in disease progression - skin cells, immune cells, and the microbiota”, says research leader and center director, prof Niels Ødum. The group builds on multidisciplinary collaboration between basic, translational, and clinical researchers. The techniques and models span from molecular, genetic, single cell sequencing, advanced flow cytometry, imaging, and cellular approaches to 3D and animal models as well as patient ex vivo models, human skin models, and clinical trials. Together with partners at the Department and the Health Science Faculty, Danish University Hospitals, as well as International academic and industrial collaborators, we create a unique platform to study specific disease mechanisms and therapy at all levels from molecule to the patient in question.