Immune checkpoint ligands such as PD-L1, CTLA-4, TIM-3, and LAG-3 expressed by tumour and immunosuppressive cells engage with their respective receptors on CAR-T cells, suppressing activation, reducing cytokine production, promoting dysfunction, and ultimately limiting persistence and anti-tumour efficacy (Fig. 2B) [175–177]. The gene discussed is HAVCR2; the disease is neoplasm.