Activation of the STING Pathway in B-cell Lymphoma Cell Lines

Abstract

Follicular lymphoma, a subtype of non-Hodgkin lymphoma (NHL), often presents challenges in patient management due to treatment resistance and relapse. The STING (Stimulator of Interferon Genes) pathway of the immune system has attracted attention as a possible target for cancer treatment. Promoting anti-tumor responses, the STING pathway activates both innate and adaptive immunity. Using cyclic di-adenosine monophosphate (CDA), a known STING agonist, this research investigates the activation of the STING pathway in B-cell lymphoma cell lines (RAJI, OCI-Ly19, HG3, MAVER-1, and PCL12) relative to a control monocyte cell line (THP-1). We evaluated protein expression of key signaling molecules (STING, TBK1, and IRF3) and their phosphorylated forms using Western blot analysis, cytokine production through qPCR and ELISA, and cytokine secretion levels via enzyme-linked immunosorbent assay (ELISA). Results revealed that although the monocyte control cell line THP-1 showed strong STING pathway activation—shown by elevated phosphorylation of STING, TBK1, and IRF3 and higher production of cytokines TNFα and IFN-β. The B-cell lymphoma lines showed limited or absent STING activation. Specifically, the OCI-Ly19 and HG3 cell lines showed some response in protein expression but failed to produce significant cytokine responses. These results underline the need of more study on the molecular mechanisms controlling STING dysfunction in lymphomas since they imply that B-cell lymphomas may have defects in the STING pathway, which may lead to immune evasion.