Various mechanisms underlying primary or acquired resistance to ICIs in NSCLC have been proposed, providing a biological rationale for therapeutic strategies to overcome resistance, including a combination of ICIs with anti-angiogenic drugs, tumor microenvironment modulators, adhesion molecules, or novel ICIs targeting different pathways beyond CTLA-4 and PD-1/PD-L1, such as TIGIT [25]. The gene discussed is CTLA4; the disease is neoplasm.