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MINI REVIEW article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1555491
Activation-Induced Cytidine Deaminase in Tertiary Lymphoid Structures: Dual Roles and Implications in Cancer Prognosis
Provisionally accepted- Xinxiang Medical University, Xinxiang, China
Activation-induced cytidine deaminase (AID) serves as a critical molecular orchestrator in the germinal center (GC) reaction within secondary lymphoid organs (SLOs), driving the production of high-affinity antibodies through somatic hypermutation. While its pathological implications are well-documented -including ectopic expression in non-B cell populations and transcriptional dysregulation linked to hematological malignancies and solid tumorigenesis -the cellular provenance of AID in solid tumors remains an unresolved paradox. This review advances two principal hypotheses: (1) AID may derive from tertiary lymphoid structures (TLSs), ectopic immune niches mirroring SLO organization, and (2) exhibits context-dependent transcriptional duality, capable of both potentiating and suppressing gene expression based on microenvironmental cues.Through systematic analysis of AID/GC involvement across cancer subtypes, we delineate mechanistic connections between lymphoid neogenesis and tumor progression. Our examination extends to TLS architecture, revealing three critical dimensions: (i) structural organization and cellular heterogeneity, (ii) developmental trajectories, and (iii) bidirectional interactions with tumor microenvironments. Crucially, we establish functional parallels between tumor-infiltrating B cells (TIL-Bs) in SLOs versus TLSs, while elucidating the differential roles of AID in canonical GC versus TLS-associated GC formation. This synthesis ultimately proposes that AID's functional dichotomy -acting as both oncogenic collaborator and tumor suppressor -underlies the paradoxical prognostic associations observed with TLS presence across malignancies. The review thereby provides a conceptual framework reconciling AID's dual functionality with the context-dependent immunobiology of tumor-associated lymphoid structures.
Keywords: activation-induced cytidine deaminase (AID), germinal center reaction, TLSs, TIL-B cells, solid tumors
Received: 04 Jan 2025; Accepted: 25 Mar 2025.
Copyright: © 2025 Zhuangwei, Jiao, Xue, Shi, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Junna Jiao, Xinxiang Medical University, Xinxiang, China
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