Summary of work Not all patients respond to checkpoint inhibitor therapy, and researchers seek to understand why. Senior authors Robert Schreiber, PhD, a Parker Institute researcher, and Maxim Artyomov, both of Washington University in St. Louis used single cell analysis to compare the tumor microenvironment in patients who responded and didn’t respond to treatment with anti PD-1, anti CTLA-4 or the combination. What they discovered were dynamic changes in essential, but different components of the immune system – not only in the lymphoid compartment, which is the target of the checkpoint inhibitor treatment and provides long lasting immune protection, but also in the myeloid compartment, which is a complex system that can either stimulate or inhibit immune responses against cancer. These results indicate that targeting specific components in each compartment could improve the efficacy of checkpoint therapy in more cancer patients. Why this is impactful to patients “This study gives insight to improving checkpoint inhibitor therapy by targeting myeloid and lymphoid cells,” says Samantha Bucktrout, PhD, director of research at PICI. “Work remains to bridge these findings in mice to patients, but deep characterization of dynamic immune responses during successful immunotherapy provides an important framework for advancing cancer immunotherapy.”