COLD SPRING HARBOR, N.Y., Nov. 8, 2016 /PRNewswire/ -- One of the worst cruelties of lethal cancer is the phenomenon called wasting, or in medical terms, cachexia (pronounced ka-CHEX-ia), in which a patient seems literally to diminish in bodily terms as the cancer ravages one or more internal organs. Today, a team at Cancer Research UK Cambridge Institute, led by Professor Douglas Fearon, M.D., of Cold Spring Harbor Laboratory in New York and a Distinguished Scholar of the Lustgarten Foundation, publishes in Cell Metabolism results of experiments showing that tumors interfere with the patient's ability to cope with wasting and may even impair their ability to respond to immunotherapy. In mouse models of human pancreatic and colon cancer, the team traces cachexia to a molecular reprogramming of the liver induced by the tumor, the effect of which is to alter the liver's normal response to caloric deficiency. As the caloric deficiency worsens and weight continues to decline, the body responds by releasing stress hormones. The team found that these hormones, in turn, prevent the immune system from responding to the tumor. The researchers performed experiments demonstrating that in mouse models of pancreas and colon cancer, liver reprogramming begins during pre-cachexia, when wasting has just begun but is not yet manifest. Signals broadcast by tumor cells induce the release of interleukin 6 (IL-6), a molecular beacon of the immune system called a cytokine, that normally helps induce an immune response. IL-6, in turn, impairs the capacity of the liver to respond to caloric deprivation, which is already under way in pre-cachectic mice. "Translated into human terms, this means that when a cancer patient loses his or her appetite and decides not to eat, the liver is not going to generate sufficient energy to compensate for the caloric loss," explains Dr. Fearon.