Modulation of T-cell responses with biologics has been one of the greatest advances in medicine in the last decade.1–3 We now have a better understanding of T-cell biology and are able to fine-tune T-cell responses with different treatment options in cancer and autoimmunity.4,5 Some examples of treatment modalities include checkpoint inhibitors such as α-PD-L1 antibodies in cancer and a CTLA-4 Ig protein for the treatment of autoimmune conditions.6,7 In cancer and autoimmunity, T-cell activation is dysregulated in opposite ways. The gene discussed is CD274; the disease is Autoimmunity.