STING is Expressed by Hodgkin and Reed Sternberg (HRS) Cells in a Subset of Classical Hodgkin Lymphoma (cHL) and Correlates with Tumor Microenvironment and Immune Response

Introduction: Cytosolic DNA of exogenous or endogenous origin triggers activation cyclic GMP-AMP synthase (cGAS), a cytosolic sensor, that activates innate immune responses through the adaptor protein STING. The latter, in turn, TBK1 and IKK kinases that, activate IRF3 NF-κB transcription factors, which induce expression interferons (IFNs), chemokines cytokines involved anti-tumor responses. patterns STING Hodgkin Reed-Sternberg (HRS) cells potential role cGAS-STING pathway classical lymphoma (cHL) remain unknown to date. Methods: In this prospective study, was immunohistochemically analysed cohort 52 previously untreated patients with cHL available tissue for flow cytometry (FC) analysis histology as well peripheral blood samples FC. An arbitrary 10% cutoff used positivity HRS. vitro system included 6 cell lines (MDAV, L1236, L428, L540, HDLM2, KMH2). Gene (mRNA level) expression/activation components at baseline experimental conditions were by quantitative RT-PCR (RT-qPCR) Western blot, respectively. treated agonist subjected silencing gene using transient transfection specific siRNA construct. cGAS-STING-associated IFNs cytokines, including IFN-β, CXCL10, IFN-γ, STING, control (GAPDH), RT-qPCR. Results: positive HRS 22 (42%) patients. significantly correlated lower numbers STING+ T-lymphocytes (p < 0.0001) CD3+ = 0.04) but higher CD20+ B-cells assessed FC tissues. presentation, T-cells 0.005) NK-cells 0.02). did not correlate clinical features age, gender, Ann Arbor stage, B-symptoms, tumor burden, bulky disease, anemia, other hematologic values. mRNA level substantially L428 HDLM2 compared lines. Treatment agonists stimulated IFN-β and/or CXCL10 variable indicating functional Knocking down resulted dramatic increase cells. Conclusions: is expressed subset correlates lymphocytic populations microenvironment blood. suggesting may have therapeutic implications cHL. Keywords: Diagnostic Prognostic Biomarkers, lymphoma, Microenvironment No conflicts interests pertinent abstract.