New Insights Into the Role of Neutrophils in Lymphoma.

Under physiological conditions, neutrophils exhibit remarkable tissue surveillance capabilities, infiltrating interstitial spaces within secondary lymphoid organs such as lymph nodes and spleen, and even actively patrolling nodal tissues. These observations provide groundbreaking insight into the functional heterogeneity of neutrophils while offering new perspectives on the tumor microenvironment (TME) in lymphomas. A critical question arises: what roles might these specialized, lymphoid tissue-resident neutrophils play in lymphomagenesis through their unique phenotypic and functional adaptations? Although tumor-associated neutrophils have been extensively studied in solid tumors for their contributions to immunologically heterogeneous microenvironments that promote tumor progression, metastasis, and therapy resistance, the distinct biology of neutrophils within lymphoid organs has historically been overlooked. This knowledge gap has resulted in limited exploration of lymphoma-associated neutrophils, despite the shared hematopoietic origin of lymphomas and neutrophils. Herein, we aim to integrate current understanding of neutrophil physiology in lymphoid tissues with emerging evidence of their pathological involvement in lymphomas, while proposing potential neutrophil-targeted therapeutic strategies for lymphoid malignancies. By bridging these research domains, we seek to establish a conceptual framework for investigating neutrophil-lymphoma interactions, and to highlight their therapeutic implications in the era of TME modulation.