STAT3 and NF-κB are Simultaneously Suppressed in Dendritic Cells in Lung Cancer

Abstract

Tumour-induced dendritic cell (DC) dysfunction plays an important role in cancer immune escape. However, the underlying mechanisms are not yet fully understood, reflecting the lack of appropriate experimental models both in vivo and in vitro. In the present study, an in vitro study model for tumour-induced DC dysfunction was established by culturing DCs with pooled sera from multiple non-small cell lung cancer (NSCLC) patients. The results demonstrated that tumour-induced human monocyte-derived DCs exhibited systematic functional deficiencies. Transcriptomics analysis revealed that the expression of major functional cluster genes, including the MHC class II family, cytokines, chemokines, and co-stimulatory molecules, was significantly altered in tumour-induced DCs compared to that in control cells. Further examination confirmed that both NF-κB and STAT3 signalling pathways were simultaneously repressed by cancer sera, suggesting that the attenuated NF-κB and STAT3 signalling could be the leading cause of DC dysfunction in cancer. Furthermore, reversing the deactivated NF-κB and STAT3 signalling could be a strategy for cancer immunotherapy.

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

“…(TLR)-induced proinflammatory mediators (Park et al, 2004;Kitamura et al, 2005;Cheng et al, 2008;Melillo et al, 2010;Wölfle et al, 2011); and 5) increased tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase and resultant T cell apoptosis mediated by kynurenine, a tryptophan metabolite (Barton, 2006). These STAT3 effects are mediated by pY-STAT3; inhibition of JAK/STAT3 signaling improves mature DC function and augments antitumor immunity (Nefedova et al, 2004(Nefedova et al, , 2005a, although attenuating STAT3 and NF-kB signaling in immature DCs leads to systemic DC dysfunction in non-small cell lung cancer (NSCLC) (Li et al, 2017). 4.…”

Interleukin‐33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development

“…Human peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of healthy donors at the Blood Centre of Anhui Province using Ficoll–Hypaque (Solarbio, P4350) density gradient centrifugation NK cells in PBMCs were further purified using human NK Cell Isolation Kit (Miltenyi Biotec, 130‐092‐657) following manufacturer's instructions (purity >95%). Isolated NK cells were cultured in RPMI medium supplemented with 10% FBS, penicillin and streptomycin.…”

Identification of a Prognostic Model Based on Immune-Related Genes of Lung Squamous Cell Carcinoma

“…These results showed that DEIRGs in prediction model could act as predictor for predicting immunocyte infiltration in LUSC. A study demonstrated that STAT3 and NF-κB signaling pathways were simultaneously attenuated in dendritic cells of lung cancer (48). A study showed that the tumor-associated CD66b neutrophils were correlated with adverse prognostic factors of NSCLC (49).…”