Cancer cachexia might lead to failures with immunotherapies

Researchers at the Cancer Research UK Cambridge Institute have discovered a weight loss condition in cancer patients may be the reason immunotherapy fails in certain patients.

Cancer cachexia, leading to a loss of appetite and weight loss in cancer patients, affects patients in different ways at different rates, often occurring. With immunotherapy relying on the activation of the body’s own cells, such treatment cannot take place in cachexia patients due to the lack of energy sources.

Research, published in the journal Cell Metabolism, found that in the earliest stages of cancer in mice, without the presence of cachexia, a protein released by cancer changes the way the liver processes nutrient stores. This change affects how patients maintain a healthy weight and storing the energy supply needed to react with immunotherapy.

"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, a PhD student from the University of Cambridge School of Clinical Medicine and co-first author of the study. "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."

Researchers encouraged additional studies looking to use this knowledge to benefit patients with cancer.

"Cancer immunotherapy might completely transform how we treat cancer in the future—if we can make it work for more patients," said Tobias Janowitz, MD, medical oncologist at the 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."