Myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies characterized by excessive proliferation of mature blood cells, predisposition to thrombosis, and potential evolution to acute leukemia or myelofibrosis. Classical Ph-negative MPNs are largely driven by JAK2v617f, CALR, and MPL mutations (Vainchenker and Kralovics, 2017). The most common genetic aberration is the JAK2v617f mutation, present in a majority of patients with polycythemia vera (PV) and a significant proportion of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Despite advances in targeted therapies, disease progression and therapeutic resistance remain significant clinical challenges.

In recent years, immunotherapy has emerged as a transformative treatment approach in various malignancies, particularly hematologic cancers (Tang et al., 2023). Mounting evidence suggests that tumor initiation and progression are closely associated with immune dysregulation, characterized by abnormal numbers and impaired functionality of immune cells. Dendritic cells (DCs), critical antigen-presenting cells, play a pivotal role in initiating and regulating T cell-mediated anti-tumor immunity. Dysfunctional DC-T cell interactions can severely compromise anti-tumor immune surveillance, enabling tumor persistence and progression. Clinical studies have shown that correcting DC dysfunction or enhancing DC-mediated T cell responses can significantly improve therapeutic outcomes in several hematologic malignancies, including acute myeloid leukemia and lymphoma (Waldman et al., 2020).

However, the precise immunological mechanisms underpinning MPNs, especially concerning the JAK2v617f mutation, remain inadequately understood. Recent studies highlight distinct immune profiles associated with different driver mutations such as JAK2v617f, CALR, and MPL. Notably, JAK2v617f-positive MPN patients exhibit pronounced immune dysregulation characterized by chronic inflammation and elevated cytokine production compared to CALR- or MPL-mutant patients (Haage et al., 2024, Strickland et al., 2022). This altered immunological landscape contributes to the unique clinical trajectory and therapeutic response patterns observed in JAK2v617f-positive MPNs.

Whether similar immune dysfunction occurs in MPN patients remains unclear. The JAK2v617f mutation, in particular, is not fully understood in terms of its impact on the immune system. This study aims to explore how the JAK2v617f mutation influences immune dysfunction and contributes to immune evasion in MPNs. By evaluating the quantity and functionality of DCs and T cells in JAK2v617f-positive patients, we seek to identify critical immune characteristics within the tumor microenvironment. Additionally, using mouse models, we will investigate mechanisms of immune dysfunction and identify potential therapeutic targets.