Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma

Abstract

Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n = 390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r = −0.36), IL-12 (r = −0.17), IP-10 (r = −0.23), and MIG (r = −0.32) concentrations (p < 0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77–4.07, p < 0.001), elevated AMC (OR 2.05, 95% CI 1.34–3.14, p < 0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31–5.34, p < 0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48–3.49, p < 0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03–2.28, p = 0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.