On matched patient-derived organotypic tumor spheroids (PDOTS) and matched patient-derived organoids (PDOs) that mimic TME, targeting innate immune kinase TANK-binding kinase 1 (TBK1) (an immune evasion gene) enhances response to PD-1 blockade by lowering the cytotoxicity threshold to effector cytokines (TNFα/IFNγ) thereby overcoming resistance to cancer immunotherapy 35. The gene discussed is TBK1; the disease is cancer.