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

作者：Binder Moritz; O' Byrne Megan M; Maurer Matthew J; Ansell Stephen; Feldman Andrew L; Cerhan James; Novak Anne; Porrata Luis F; Markovic Svetomir; Link Brian K; Witzig Thomas E

来源：American Journal of Hematology, 2017, 92(8): 752-758.

DOI：10.1002/ajh.24758

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.

• 出版日期2017-8