In Sickness and Health: The Role of Trained Immunity

Trained immunity is a functional state of the innate immune response and is characterized by long-term epigenetic reprogramming of innate immune cells. Although initially reported in circulating monocytes and tissue macrophages, subsequent findings indicate that immune progenitor cells in the bone marrow can also be trained, explaining its long-term effects. Although trained immunity is beneficial in different immune scenarios (fighting infections, vaccination boosts, etc), it’s inappropriate induction can lead to aberrant inflammation resulting in various pathological conditions. Trained immunity is triggered by the recognition of pathogen-associated molecular patterns by pattern recognition receptors (TLR, NLR, RLRs, etc), followed by the modulation of the cytokine environment and the subsequent metabolic and histone modifications generating innate immune memory. Trained immunity involves various molecular pathways, resulting in distinct types of immune memory. Examples are pathways that include the interferon (IFN)-related, NF-kB-driven, and mTOR-dependent responses. These different pathways collectively support the innate immune system's ability to "remember" prior encounters, offering enhanced immune protection but also presenting risks, particularly in chronic inflammation and autoimmune conditions. The contrasting roles of trained immunity provides a new framework for the development of therapies and treatment strategies that target epigenetic and metabolic pathways of the innate immune system aiming at improving the contribution of the primary immune responses to different interventions. Further research is needed to fully understand the benefits and drawbacks of applying trained immunity to therapeutic strategies.

The central goal of this Research Topic is to provide a more complete understanding of the various (common and novel) types of trained immunity in different contexts in cancer immunity and immunotherapy. We will address both the positive and negative impacts of trained immunity on health and elucidate how its modulation can ameliorate immune responses.

To that aim, we want to compile a wide array of interdisciplinary studies exploring a comparative and multi-layered analysis of mechanisms responsible for the various types of trained immunity in oncology. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case reports, and Perspective articles that cover, but are not limited to, the following topics:

• Mechanisms supporting trained immunity in preclinical models and clinical settings
• Novel strategies to modulate trained immunity
• Mechanisms to modulate or circumvent dysfunctional trained immunity to regain immune priming and function, or to improve the success of immune interventions
• Studies highlighting the impact of prior trained immunity to subsequent immune modulations
• Studies related to the reprogramming of the progenitor cells in the bone marrow
• Combinatorial therapeutic strategies that target trained immunity reprogramming to ameliorate future interventions


Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.