Dynamic immune yin-yang in chronic myeloproliferative neoplasms mechanisms, therapeutic implications, and future...

Chronic myeloproliferative neoplasms (MPNs) are associated with dynamic and multifaceted changes in their immune microenvironment. Throughout disease progression, the interplay between pro-inflammatory ("yang") and immunosuppressive ("yin") cytokines and immune cells shapes the immune milieu and drives clinical progression. Sustained production of pro-inflammatory cytokines-such as interleukin-6 (IL-6) and interleukin-1β (IL-1β)-promotes clonal expansion and accelerates disease progression. Conversely, immunosuppressive mediators, including transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), allow malignant clones to evade immune surveillance through the suppression of effector T-cell and natural killer (NK) cell cytotoxic functions. This dualistic immune state, with hyperactivation in early disease and immunosuppression in advanced stages, reflects the clinical and biological heterogeneity observed in MPNs. Emerging immunomodulatory therapies-such as interferon-α, Janus kinase (JAK) inhibitors, and other immunoregulatory agents-have demonstrated efficacy primarily by restoring immune balance. This review outlines the dual roles of immune cells and cytokines in MPN pathophysiology, emphasizes the significance of immune yin-yang imbalance, and evaluates current and prospective immunotherapeutic strategies for targeted immunologic intervention.