While colitis development following anti-PD-1 treatment is less common (2% of patients) compared with anti-CTLA4 (11%) in clinical studies, the combination of the two immunotherapies increases both the incidence (13%) and severity of colitis in patients with melanoma.4 Notably in our model, monotherapy anti-PD-1 treatment does not elicit gut inflammation but exacerbates the colitogenic effects of Fc-effector anti-CTLA4. The gene discussed is PDCD1; the disease is melanoma.