Weight loss may make cancer immunotherapies ineffective

A weight loss condition that affects cancer patients may make immunotherapy ineffective, according to a new study which explains why the approach boosting a patient's immune system to treat the disease fails in a lot of people.
Cancer immunotherapies involve activating a patient's immune cells to recognise and destroy cancer cells.
They have shown great promise in some cancers, but so far have only been effective in a minority of patients with cancer. The reasons behind these limitations are not clear.
Researchers at the University of Cambridge have found evidence that the mechanism behind a weight loss condition which affects patients with cancer could also be making immunotherapies ineffective.

The condition, known as cancer cachexia, causes loss of appetite, weight loss and wasting in most patients with cancer towards the end of their lives.
However, cachexia often starts to affect patients with certain cancers, such as pancreatic cancer, much earlier in the course of their disease.

Scientists found that that even at the early stages of cancer development in mice, before cachexia is apparent, a protein released by the cancer changes the way the body, in particular the liver, processes its own nutrient stores.
"The consequences of this alteration are revealed at times of reduced food intake, where this messaging protein renders the liver incapable of generating sources of energy that the rest of the body can use," said Thomas Flint, from the University of Cambridge School of Clinical Medicine.

"This inability to generate energy sources triggers a second messaging process in the body - a hormonal response - that suppresses the immune cell reaction to cancers, and causes failure of anti-cancer immunotherapies," Flint said.
"Cancer immunotherapy might completely transform how we treat cancer in the future - if we can make it work for more patients," said Tobias Janowitz, from University of Cambridge.
"Our work suggests that a combination therapy that either involves correction of the metabolic abnormalities, or that targets the resulting hormonal response, may protect the patient's immune system and help make effective immunotherapy a reality for more patients," said Janowitz.

"If the phenomenon that we have 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 Duncan Jodrell, from the Cambridge Cancer Centre.
"Understanding the complicated biological processes at the heart of cancer is crucial for tackling the disease - and this study sheds light on why many cancer patients suffer from both loss of weight and appetite, and how their immune systems are affected by this process," said Nell Barrie, from Cancer Research UK.

The research was published in the journal Cell Metabolism.