Weight loss condition provides clue to why some immunotherapy treatments fail

A weight loss condition frequently seen in cancer patients could provide answers as to why certain immunotherapy treatments fail in some patients. 

Immunotherapy drugs work by turning the body’s immune system on cancer. 

And while the treatments have shown great promise for some patients with certain cancers, they don’t work for everyone. 

Now, researchers at the Cancer Research UK Cambridge Institute at the University of Cambridge have found that a weight loss condition that affects cancer patients could be making immunotherapies ineffective. 

The condition – called cancer cachexia – causes loss of appetite, weight loss and wasting in many patients with cancer towards the end of their lives.

The condition can affect patients with certain cancers, such as pancreatic cancer, much earlier in the course of their disease.

The new research – published in the journal Cell Metabolism – looked at mice with early stage cancer, before cachexia was apparent.

Cancer cells in these mice released a molecule that changed how organs, particularly the liver, processed nutrient stores. 

The molecule – called Interleukin-6 – stops the liver generating the energy the rest of the body needs when food intake is low. 

The inability to generate energy caused a hormonal response that stops the immune system reacting to cancer, and caused the failure of immunotherapies in mice.

Dr Tobias Janowitz, from the Department of Oncology at the University of Cambridge and who co-led the study, said finding a way to correct the metabolic changes could make immunotherapy work in more patients. 

But the team first need to test if the same process occurs in people. 

“If the phenomenon that we’ve described helps us to divide patients into likely responders and non-responders to immunotherapy, then we can use those findings in early stage clinical trials to get better information on the use of new immunotherapies,” said Professor Duncan Jodrell, director of the Early Phase Trials Team at the Cambridge Cancer Centre and co-author of the study.

Nell Barrie, senior science information manager at Cancer Research UK, said the study shed light on why many cancer patients experience both loss of weight and appetite, and how their immune systems are affected by this process. 

“Although this research is in its early stages, it has the potential to help make a difference on both fronts – helping treat weight loss and also improving treatments that boost the power of the immune system to destroy cancer cells,” she added.