Ping-Chih Ho, Ludwig Lausanne Associate Member Photo Credit: Ludwig Cancer Research |
A Ludwig Cancer Research study has discovered that the immune system’s surveillance of cancer can itself induce metabolic adaptations in the cells of early-stage tumors that simultaneously promote their growth and equip them to suppress lethal immune responses.
Led by Ludwig Lausanne Associate Member Ping-Chih Ho and published in Cell Metabolism, the study details the precise mechanism by which this “immunometabolic editing” of emergent tumors occurs in mouse models of the skin cancer melanoma and identifies a novel biochemical signaling cascade and proteins that orchestrate its effects. Aside from illuminating a previously unknown dimension of tumor evolution, the findings hold significant promise for improving the efficacy of cancer immunotherapy.
“We have uncovered dozens of metabolic enzymes that contribute to immune evasion in melanoma tumors,” said Ho. “These enzymes, as well as some of the individual components of the signaling pathway we’ve identified, represent a rich trove of potential drug targets to undermine the defenses erected by immunometabolic editing. Such drugs could make tumors vulnerable to immune clearance and could also be used in combination with checkpoint blockade and other immunotherapies to overcome the resistance most cancers have to such treatments.”