In a recent study by Perez-Ruiz et al., the authors show that prophylactic blockade of TNF ameliorates colitis but enhances tumor immunity in mice.255 TNF blockade is a well-established treatment option for multiple autoimmune diseases, including rheumatoid arthritis, psoriasis and IBD.256 Furthermore, TNF blockade is used in patients developing irAEs following immune checkpoint blockade that are refractory to steroids.257 In this study the authors show that the dual treatment with anti-CTLA-4 and anti-PD-1 mAbs worsens DSS-induced colitis. This evidence concerns the gene CTLA4 and colitis.