STAT6 activation correlates with cerebrospinal fluid IL-4 and IL-10 and poor prognosis in primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma with a dismal outcome in the majority of cases. In clinical practice, prognosis is estimated through clinical risk scoring, which can help in guiding the appropriate management. However, there is no established biomarker to track treatment response and relapse. Here, we showed that tumor expression of activated STAT6 (pSTAT6) correlates with cerebral spinal fluid (CSF) levels of its activator interleukins, IL-4 (r 0.62, p=0.013) and IL-10 (r 0.97, p= <0.001), suggesting their potential use as surrogate biomarkers of JAK/STAT activation. Elevated CSF cytokines levels were significantly associated with a shorter progression free survival (IL-4 HR 2.02, 95% CI 1.07-2.99; IL-10 HR 3.32, 95%CI 1.18-1.84), and presented a positive trend with inferior overall survival (IL-4 HR 1.75, 95% CI 0.93-2.45; IL-10 HR 2.09, 95%CI 0.89-1.43). In addition, CSF IL-4 and IL-6 levels correlated with response to therapy and relapsed disease. These results indicate that the CSF levels of IL-4 and IL-10 may be useful biomarkers of prognosis and disease activity in patients with PCNSL.