Mechanistically, anti-TIM-3 mAbs (i) disrupt Galectin-9/PtdSer signalling to relieve dendritic-cell paralysis and potentiate IL-12-driven T-cell responses; (ii) leverage Fc-mediated ADCC/ADCP to eradicate TIM-3+ tumour cells and (iii) spare T-cell intrinsic inhibition, predicting reduced collateral toxicity. Here, HAVCR2 is linked to neoplasm.