In an interview conducted during the 2021 European School of Hematology (ESH) 7th Translational Research E-Conference on Myelodysplastic Syndromes, Shahram Kordasti, MD, PhD, King’s College London, London, UK, discusses TP53 mutations in patients with MDS and the immunological impact of these mutations on prognosis. Recent data demonstrate that TP53 can expand a specific subset of ICOS-positive Tregs, which also contributes to further immune suppression. Therefore, the immune system is more compromised and contributes to worse prognosis.