It has been described in mice models that Primary Myelofibrosis (PMF) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes. To prove this hypothesis, we quantified PD-L1 expression on 29 bone marrow (BM) biopsies. We created a scoring system to quantify PD-L1 expression in megakaryocytes. We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared to the control group with a score of 212.6 vs 121.1 (t-value 2.05,p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared to the control group with score of 205.9 vs 121.1(t-value 2.12,p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative vs the control group 187.2 vs 121.1 (t-value 1.02,p-value 0.162). These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared to the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.

Background: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS. Aims: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy / fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy. Methods and Results: Patients >18-years-old with rHGG (WHO grade III and IV) receiving ICI+SBRT or ICI monotherapy between 1/1/16-1/1/19 were included. Adverse events, 6-month PFS and overall survival (OS) were assessed. Log-rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast-enhanced magnetic resonance perfusion metrics were performed. Twenty-one patients with rHGG (ICI+SBRT: 16; ICI: 5) were included. The ICI+SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3-5 AEs in the ICI+SBRT group, and four grade 1 and no grade 2-5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI+SBRT and ICI groups; median OS was 7 and 6 months among ICI+SBRT and ICI groups, respectively. There were significant differences in pre- and post-treatment tumor volume in the cohort (12.35 vs. 20.51; p=0.03), but not between treatment groups. Conclusions: In this heavily pretreated cohort, ICI with re-irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re-irradiation with ICI+SBRT in rHGG.