Hematologic malignancies, including leukemia, lymphoma, and myeloma, present considerable clinical challenges, driven in part by their unique tumor microenvironments and the ability of cancer cells to evade immune surveillance. Within these malignancies, macrophages are key components of the tumor microenvironment, substantially influencing disease progression and modulating the immune landscape. Emerging research has highlighted the potential of macrophage-targeted therapies as a novel approach for treating these cancers. Despite promising advances, there remain significant knowledge gaps regarding the diverse roles of macrophages and their intricate interactions within the tumor microenvironment.
Early-stage investigations are developing a range of therapeutic modalities—including small molecules, monoclonal antibodies, and immunomodulatory agents—that aim to modulate macrophage activity to achieve therapeutic benefits. However, additional research is essential for elucidating the mechanisms by which macrophages can be reprogrammed to acquire a pro-inflammatory, anti-tumoral phenotype and to evaluate the therapeutic potential and limitations of combining macrophage-targeted strategies with established treatments.

This Research Topic aims to advance the field by providing a comprehensive overview of macrophage-targeted therapies in hematologic malignancies. It seeks to address critical questions regarding macrophage dynamics within the tumor microenvironment and to investigate how reprogramming macrophage phenotypes might enhance anti-cancer responses. Additionally, this collection focuses on the translational impact of macrophage-targeted approaches, including biomarker discovery for patient stratification and the assessment of clinical outcomes for safety, efficacy, and quality of life.

Contributions are encouraged in the following areas:
• Mechanistic insights into the functions of macrophages within the tumor microenvironment of hematologic malignancies.
• The design, development, and preclinical/clinical evaluation of novel macrophage-targeting agents.
• Therapeutic strategies for reprogramming macrophages to adopt a pro-inflammatory, anti-tumoral state.
• Investigation of combinatorial approaches that integrate macrophage-targeted therapies into chemotherapy-, radiation-, or immune-based treatments, targeting potential synergies and resistance mechanisms.
• Biomarker identification and validation to optimize patient selection for macrophage-targeted interventions.
• Analyses of clinical trial outcomes and real-world data on macrophage-targeted therapies, emphasizing safety, efficacy, and impacts on patients’ quality of life.

Scope Note: Manuscripts that rely exclusively on bioinformatic or computational analyses of public genomic or transcriptomic datasets, without accompanying biological validation in relevant in vitro, in vivo, or clinical settings, are outside the scope of this collection.

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Frontiers in Immunology

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