Kidney Tumors Reprogram Their Metabolism to Evade the Immune System

Controlling renal cell carcinoma's (RCC) metastatic growth has been a challenge for genitourinary oncologists, and a new study demonstrates how this cancer reprograms its environment to bypass the immune system.

Researchers at the University of California Davis Comprehensive Cancer Center used both proteomics-a study of proteins, particularly their structures and functions-and metabolomics to learn how RCC reprograms its metabolism.¹

Robert Weiss, MD, professor of nephrology and internal medicine at UC Davis and chief of nephrology at the VA Northern California Health System in Sacramento, and his team analyzed human RCC tissue. They used combined grade-dependent proteomics and metabolomics analysis to determine how metabolic reprogramming occurs in this disease, and how allows it to escape available therapeutic approaches. The research team discovered that the cancer tumor reprograms its environment to minimize the immune response. This game-changing discovery, which was published in the May 2015 issue of Cancer Research, will likely lead to new therapies.²

“The mortality for someone with highly metastatic RCC is somewhere in the 90% range,” said Dr. Weiss in a UC Davis press release. “We now know this cancer is actually reprogramming its environment to minimize the immune response."¹

Cancer is diagnosed and explained in terms of stage and grade, and this study also found that cancer grade affects this reprogramming in a big way. Understanding how much a tumor has metastasized is as important as finding out how abnormal the cancer cells have become. The researchers noted that in RCC, higher-grade cancers were remodeling their environments more aggressively compared to low-grade cancers.

This research points to new therapeutic targets, such as the tryptophan and glutamine pathways, which could help clinicians unleash the immune system against RCC and stop these particular tumors from creating immunosuppressive metabolites.

Now that researchers are aware of this, they can begin to develop new therapeutic regimens to address these issues.

References:

• UC Davis Comprehensive Cancer Center. (2015). Revealing kidney cancer's secret.
• Wettersten HI, Hakimi AA, Morin D, et al. (2015). Grade-Dependent Metabolic Reprogramming in Kidney Cancer Revealed by Combined Proteomics and Metabolomics Analysis. Cancer Research.