Summary of work Early studies in mice suggest that treatment with checkpoint inhibitors before surgery in melanoma patients could be beneficial. This study, led by PICI investigator Jennifer Wargo, MD, of MD Anderson Cancer Center, was one of the first of its kind in patients to test this hypothesis. The study demonstrated that combining anti-PD-1 and CTLA-4 checkpoint blockade before surgery produced a better response than anti-PD-1 alone, but at the expense of significant toxicity to the patient. Due to the side effects, investigators re-designed the study to explore the safety and efficacy of anti-PD-1 plus an inhibitor of the LAG3 immune checkpoint, which they believe may be more effective than the single agent and less toxic than the original combination. Other co-authors include PICI co-director Padmanee Sharma, MD, PhD, and PICI director James Allison, PhD, at MD Anderson Cancer Center. PICI informatics scientists Christine Spencer, PhD, Danny Wells, PhD, and Robin Kageyama, PhD, are also co-authors of the paper. Why this is impactful to patients “With a patient population as high-risk as this one, it is critical to thoroughly test new interventions and gather high-quality data so that the field can move towards helping these patients who, with current standard of care options, are very likely to have their cancer recur,” PICI scientist Christine Spencer, PhD, and a co-author of the study explains. “This trial demonstrates potential limitations and opportunities to pre-surgery treatment with checkpoint blockades and was also helpful in exposing novel biomarkers that may be involved in responders.”