Introduction
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by constitutional activation of the JAK-STAT signaling pathway and bone marrow (BM) fibrosis which leads to decreased peripheral blood counts, pro-inflammatory state, and a potential for transformation to acute myeloid leukemia (AML). The median age at presentation is 65 years [2,3]. JAK2-V617F is the most common mutation in PMF and is found in 50-60% of patients [4]. The only curative treatment option currently available is allogeneic stem cell transplant. However, most patients are ineligible because of advanced age and comorbidities [5]. Ruxolitinib and fedratinib, JAK2 inhibitors, are the only FDA approved treatment for intermediate/high risk PMF patients [6,7]. However, those drugs have their limitations and only improve symptoms and decrease splenomegaly, without an overall survival benefit [6,7]. Therefore, there is a significant unmet need for treatment options in this patient population.
Prestipino et al. discovered that mice models with JAK2-V617F mutated MPN generally have an increased expression of PD-L1 that leads to cancer immune evasion by inhibiting the antitumor effect of the T lymphocytes against cancer cells [1]. Checkpoint inhibitors are monoclonal antibodies that block the interaction between PD-L1 and its receptor, allowing the immune system to fight cancer cells with an enhanced antitumor response. Pembrolizumab was the first checkpoint inhibitor approved by the FDA for patients with metastatic non-small-cell lung cancer with >50% PD-L1 expression in tumor cells by immunohistochemistry stain. In this subset of patients, pembrolizumab was more effective than systemic chemotherapy [9].
In this paper, we compared the PD-L1 expression among patients with JAK2-mutated PMF versus JAK2-unmutated PMF patients versus normal controls without no PMF or JAK2 mutation.