Trained immunity in the treatment for haematological malignancy

Trained immunity, an emerging treatment strategy, confers long-term anti-tumour memory by modulating epigenetic and metabolic reprogramming of innate immune cells, offering a novel pathway for immunotherapy of haematological malignancies. This article systematically outlines the mechanisms by which inducers such as β-glucan, Bacille Calmette-Guérin (BCG) and cytokines train key effector cells including macrophages and natural killer (NK) cells. It further analyses how ageing-encompassing both organismal ageing and cellular senescence-specifically undermines the efficacy of relevant pathways at multiple levels, from haematopoietic stem cell function and intracellular signalling to the tumour microenvironment, thereby systematically impairing the induction efficiency, durability of effect, and safety of trained immunity. Building on this, the article evaluates the clinical translation prospects and associated risks, including graft-versus-host diseases (GVHDs), of strategies such as cytokine-induced memory-like (CIML) NK cells, and proposes concrete, testable translational ideas aimed at overcoming ageing-related defects. We argue that to realise the full potential of this therapy in elderly patients with haematological malignancies, future work must focus on developing individualised training protocols capable of circumventing or reversing immunosenescence.