Cancer Immunotherapy Resistance Due to Metabolic Imbalance

Immunotherapy has been a boon to those suffering from severe cancers. The science has been so transformative that just last year, three pioneering researchers won the Nobel Prize for their discoveries in the underlying immunological mechanisms that make immunotherapy drugs possible. Though for as much success as these interventions have had, there is still a segment of the population that is resistant to the drugs and their beneficial effects, and unfortunately, scientists have had difficulties nailing down the reasons why. However now, investigators at the Dana-Farber Cancer Institute, in conjunction with researchers at the Broad Institute of MIT and Harvard, have discovered that a metabolic imbalance in some cancer patients following treatment with a checkpoint inhibitor drug, nivolumab, is associated with resistance to the immunotherapy agent and shorter survival. The chemical change, which the investigators say reflects an “adaptive resistance mechanism” by cancer cells or the immune system in response to treatment with the PD-1 antibody-drug nivolumab, was linked to worse survival in patients with advanced melanoma and kidney cancer. The greater the change—the conversion of the amino acid tryptophan to a metabolite called kynurenine—the larger the impact on survival.