CTLA4 and cancer: Malignant tumors often exploit dysregulated expression of these checkpoint molecules to evade immune destruction.1–4 Clinical targeting of CTLA-4 and the PD-L1-PD-1 axis has revolutionized cancer treatment, leading to durable responses in some patients.1–7 However, primary and acquired resistance to these immune checkpoint blockade (ICB) therapies remains a major limitation.