Suppressor of cytokine signaling 1 inhibits the maturation of dendritic cells involving the nuclear factor kappa B signaling pathway in the glioma microenvironment

Abstract

Summary Recurrence and diffuse infiltration challenge traditional therapeutic strategies for malignant glioma. Immunotherapy appears to be a promising approach to obtain long‐term survival. Dendritic cells (DCs), the most specialized and potent antigen‐presenting cells (APCs), play an important part in initiating and amplifying both the innate and adaptive immune responses against cancer cells. However, cancer cells can escape from immune surveillance by inhibiting maturation of DCs. Until the present, molecular mechanisms of maturation inhibition of DCs in the tumor microenvironment (TME) have not been fully revealed. Our study showed that pretreatment with tumor‐conditioned medium (TCM) collected from supernatant of primary glioma cells significantly suppressed the maturation of DCs. TCM pretreatment significantly changed the morphology of DCs, TCM decreased the expression levels of CD80, CD83, CD86 and interleukin (IL)‐12p70, while it increased the expression levels of IL‐10, transforming growth factor (TGF)‐β and IL‐6. RNA‐Seq showed that TCM pretreatment significantly increased the gene expression level of suppressor of cytokine signaling 1 (SOCS1) in DCs. suppressor of cytokine signaling 1 (SOCS1) knock‐down significantly antagonized the maturation inhibition of DCs by TCM, which was demonstrated by the restoration of maturation markers. TCM pretreatment also significantly suppressed T cell viability and T helper type 1 (Th1) response, and SOCS1 knock‐down significantly antagonized this suppressive effect. Further, TCM pretreatment significantly suppressed p65 nuclear translocation and transcriptional activity in DCs, and SOCS1 knock‐down significantly attenuated this suppressive effect. In conclusion, our research demonstrates that TCM up‐regulate SOCS1 to suppress the maturation of DCs via the nuclear factor‐kappa signaling pathway.

Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem‐like cells microenvironment

“…9,44 DCs are bone marrow-derived, specialized antigen-presenting cells (APCs) that function within the immune system to bridge innate and adaptive immunity. 45 As dominant APCs, DCs capture tumor antigens and present them to antigen-specific T cells via MHC glycoproteins, thereby activating naive T cells and initiating specific immune responses. 46 Upon pathogen sensing, populations of DCs in peripheral tissues become activated and migrate to the T-cell areas of draining lymph nodes (LNs), where they stimulate antigen-specific T-cell responses to initiate immunity or tolerance.…”

“…DCs are bone marrow‐derived, specialized antigen‐presenting cells (APCs) that function within the immune system to bridge innate and adaptive immunity 45 . As dominant APCs, DCs capture tumor antigens and present them to antigen‐specific T cells via MHC glycoproteins, thereby activating naive T cells and initiating specific immune responses 46 .…”

The transcription factor ZNF148 promotes the malignant transformation of dendritic cells after cross-talk with glioma stem cells by upregulating PTX3

“…DCs are bone marrow-derived, specialized antigen-presenting cells (APCs) that function within the immune system to bridge innate and adaptive immunity [32]. They are present in almost all tissues wherein they detect pathogens and process extracellular and intracellular antigens for presentation to T cells in the context of major histocompatibility complex (MHC) molecules.…”

ROS regulation in gliomas: implications for treatment strategies

“…Studies have shown that tumour-conditioned medium (TCM) collected from the supernatant of human primary glioma cells can upregulate the expression of suppressor of cytokine signalling 1 (SOCS1) in DCs and then inhibit the NF-κB signalling pathway, thereby limiting the maturation of DCs. The subsequent suppression of T-cell activity, as well as IFN-γ secretion, results in immune escape of glioma cells ( 214 ). A previous study revealed that mouse gliomas have the ability to secrete cell factors including TGF-β and IL-10 ( 215 ).…”