Multiple host intrinsic and extrinsic factors associated with ICI response and toxicity have been reported, providing insights for the development of next-generation immunotherapeutics.26 It would be advantageous if next-generation immunotherapeutics had distinct mechanisms of action compared to classical anti-PD-(L)1 and anti-CTLA-4 antibodies and showed significant single-agent anti-tumor efficacy or enhanced the efficacy and safety of classical immunotherapeutics. The gene discussed is CTLA4; the disease is neoplasm.