By targeting certain molecular mechanisms in tumors, researchers hope to build a foundation for improved immunotherapy treatments for cancer patients. Immunotherapy has changed cancer care in revolutionary ways, enabling doctors to harness the body’s natural defenses to save and improve lives. While significant progress has been made, though, some cancers have proven resistant to the treatments. To better improve understanding of the mechanisms behind these failures — and to open potential pathways to solutions — an international team of researchers led by Ohio State immuno-oncologists focused on a protein called TNF receptor-associated protein-1 (TRAP1), which helps regulate how immune cells use energy inside tumors. Cancer immunotherapy innovation at The James: How Ohio State researchers are discovering new ways to harness the body’s defenses to treat cancer. TRAP1 helps control how mitochondria (the cell’s energy centers) function. The study team found that when TRAP1 levels are reduced in certain immune cells within tumors, those cells become less effective at fighting cancer, allowing tumors to evade immune control.   “We uncover that TRAP1 expression is markedly curbed in immunosuppressive tumor-associated macrophages (TAMs, a population of white blood cells within tumors that often dampen antitumor immune responses rather than eliminate cancer),” the study team wrote in the journal Nature Immunology. Cancer clinical trials at The James: Hundreds of clinical trials are currently underway at Ohio State. Search for studies by cancer type, treatment name and more. The team hopes that blocking tumor-driven signals that cause the loss of TRAP1 will enhance anti-cancer immune responses and improve immunotherapy for cancer patients. “Our findings suggest that targeting TRAP1 could help reprogram immune cells inside tumors, potentially enabling immunotherapies to work more effectively and consistently across a broader range of cancer patients,” says Stanley Huang, PhD, corresponding author of the study and a member of the Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). “Understanding why immunotherapy fails in many patients is a major public-health challenge.” Immunotherapy is just one of the oncology fields advanced every day at Ohio State. Here’s how cancer care and research innovation is improving outcomes for today’s patients while creating tomorrow’s breakthrough treatments.