Writing recently in Science, Lo and coworkers characterized a critical role of the gut microbiota in CTLA‐4 blockade‐induced colitis, revealing that an Fc domain deficient anti‐CTLA‐4 antibody can elicit antitumor responses effectively while avoiding the induction of colitis‐like disease.1 This research opens up novel avenues for employing anti‐CTLA‐4 antibody therapy to circumvent the onset of colitis, which is often considered the Achilles' heel of what is arguably the most efficacious treatment for certain blood cancers and/or solid tumors. Here, CTLA4 is linked to colitis.