Hypoxia promotes the tolerogenic phenotype of plasmacytoid dendritic cells in head and neck squamous cell carcinoma

Abstract

Objective We aim to review the roles of plasmacytoid dendritic cells (pDCs) in head and neck squamous cell carcinoma (HNSCC) and explore the effects of hypoxia on the tolerogenic transformation of pDCs. Background pDCs, best known as professional type I interferon‐secreting cells, play key roles in immune surveillance and antitumor immunity. Recently, pDCs have been shown to be tolerogenic and correlate with poor prognosis in a variety of cancers, including HNSCC. However, it remains unclear what drives the tolerogenic transformation of pDCs in the HNSCC microenvironment. Hypoxia, a prominent hallmark of the tumor microenvironment (TME) of HNSCC, can interfere with multiple immune cells and establish an immunosuppressive TME. Methods In this review, we summarize the antitumor and protumor functions of pDCs, explore the effects of hypoxia on the migration and maturation of pDCs, and discuss related mechanisms in HNSCC. Conclusions pDCs mainly display protumor functions in HNSCC. The hypoxic TME in HNSCC can enhance the migration of pDCs and inhibit the differentiation and maturation of pDCs, promoting the tolerogenic phenotype of pDCs.

Dendritic cell subsets in cancer immunity and tumor antigen sensing

“…HIF-1α is a negative regulator of pDC differentiation in vitro and in vivo [ 223 ]. In head and neck squamous cell carcinoma (HNSCC), a hypoxic TME promoted pDC migration through the HIF-1α/CXCL12/CXCR4 pathway and induced the acquisition of a tolerogenic pDC phenotype, which was characterized by defective production of IFN-α, reduced antigen presentation abilities, and expansion of Treg cells [ 224 ]. In cervical cancer, hypoxia upregulated HMGB1 release, leading to TLR9-mediated inhibition of pDC maturation and cytokine secretion and the generation of tolerogenic pDCs [ 225 ].…”

Clinical and prognostic significance analysis of glycolysis‐related genes in HNSCC

“…31 The malignancy of HNSCC relies on hyperactivated glycolysis to meet the energetic and biosynthetic demand. 32,33 In this study, we developed a robust risk score model using 12 GHRGs to predict the prognosis of HNSCC patients, which have potential for use in clinical manifestations for convenient prognostic monitoring. Currently, a plethora of studies have established the mechanistic interplay between glycolysis/hypoxia and HNSCC, which sheds light on the prognostic prediction of HNSCC using glycolysis/ hypoxia genes.…”

“…Head and neck squamous cell carcinoma is one of the most prevalent cancers globally, characterized by its uncontrolled aggressiveness and unfavorable prognosis 31 . The malignancy of HNSCC relies on hyperactivated glycolysis to meet the energetic and biosynthetic demand 32,33 . In this study, we developed a robust risk score model using 12 GHRGs to predict the prognosis of HNSCC patients, which have potential for use in clinical manifestations for convenient prognostic monitoring.…”

Tolerogenic CD11c+dendritic cells regulate CD4+Tregs in replacing delayed ischemic preconditioning to alleviate ischemia–reperfusion acute kidney injury

“…In view of the dominance of CD11c + subset in renal inflammation, we used CD11c + DCs‐deficient mice to explore the mechanism of immune tolerance induced by CD11c + DCs. In recent years, studies have shown that Tol‐DCs play a crucial role in the treatment of various inflammatory diseases, such as autoimmune disorders, tumors, heart and kidney transplantation 10,38–40 . DC vaccine as an immune therapy in cancer and organ transplantation has made significant progress, 41,42 but the research in AKI is still lacking.…”