XPO1 inhibition and nuclear export targeting in multiple myeloma: tumor biology, immunity and clinical applications

Multiple myeloma (MM) remains an incurable plasma cell malignancy despite substantial advances in treatment, including immunomodulatory drugs, monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and CAR-T cell therapies. Although these therapeutic approaches have significantly improved patient outcomes, immune escape, disease relapse, and therapeutic resistance continue to represent major challenges.Beyond its role in regulating malignant plasma cell survival, nuclear export has emerged as an important regulator of immune homeostasis. Exportin-1 (XPO1), the principal mediator of nuclear protein export, controls the intracellular trafficking of numerous transcription factors, cytokine regulators, tumor suppressors, and signaling molecules that orchestrate both innate and adaptive immune responses. Increasing evidence suggests that dysregulated nuclear export contributes to immune evasion by altering antigen presentation, cytokine signaling, immune-cell activation, and interactions between malignant plasma cells and the bone marrow immune microenvironment. Targeting nuclear export therefore represents more than a direct anti-tumor strategy; it offers a promising opportunity to reshape anti-myeloma immunity. Recent studies indicate that XPO1 inhibition may influence T-cell activation and exhaustion, NK-cell cytotoxicity, dendritic-cell function, macrophage polarization, interferon signaling, and inflammatory pathways. These immunological effects have generated considerable interest in combining nuclear export-targeted therapies with modern immunotherapeutic approaches. As our understanding of these mechanisms continues to expand, integrating molecular immunology with translational and clinical research will be essential for developing more effective immune-based therapeutic strategies for multiple myelomaThis Research Topic aims to provide a multidisciplinary platform focused on the immunological consequences of XPO1 inhibition and nuclear export targeting in multiple myeloma. We welcome studies exploring the molecular and cellular mechanisms through which nuclear export regulates anti-tumor immunity, immune surveillance, immune escape, cytokine networks, antigen presentation, and the bone marrow immune microenvironment.Particular emphasis will be placed on investigations of innate and adaptive immune responses, immune biomarkers, mechanisms of therapeutic resistance, and novel immunomodulatory strategies targeting nuclear export pathways. Translational and clinical studies evaluating immune-related outcomes, biomarker-driven approaches, and rational combinations of nuclear export inhibitors with emerging immunotherapies are also encouraged.We welcome Original Research Articles, Reviews, Mini Reviews, Systematic Reviews, Perspectives, Clinical Trials, Real-World Evidence Studies, and Translational Research covering topics including, but not limited to:• Nuclear export regulation of innate and adaptive immunity in multiple myeloma• XPO1 biology and immune signaling pathways• Tumor-immune interactions and the bone marrow immune microenvironment• T-cell, NK-cell, dendritic-cell, macrophage, and B-cell regulation• Immune surveillance and mechanisms of immune escape• Cytokine signaling, interferon pathways, and inflammatory responses• Antigen processing and presentation associated with nuclear export• Immunomodulatory effects of XPO1 inhibition and emerging nuclear export-targeting strategies• Biomarkers predicting immune response and therapeutic resistance• Combination strategies integrating nuclear export inhibition with immunotherapies• Translational studies linking immune mechanisms with therapeutic development• Clinical investigations evaluating the immunological impact of nuclear export-targeted therapiesPlease 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.Please note Topic Editor Joshua Richter acts as consultant and/or advisory board member for Janssen, BMS, Pfizer, Karyopharm, Sanofi, Takeda, Genentech, Abbvie, Regeneron, Forus, Menarini, Kite/Arcellx, UB Therapeutics. Topic editors: Joshua Richter, Turgay Ulas Source: https://www.frontiersin.org/research-topics/82960/xpo1-inhibition-and-nuclear-export-targeting-in-multiple-myeloma-tumor-biology-immunity-and-clinical-applications