Hypoxic Transformation of Immune Cell Metabolism Within the Microenvironment of Oral Cancers

Abstract

Oral squamous cell carcinoma (OSCC) includes tumors of the lips, tongue, gingivobuccal complex, and floor of the mouth. Prognosis for OSCC is highly heterogeneous, with overall 5-year survival of ~50%, but median survival of just 8–10 months for patients with locoregional recurrence or metastatic disease. A key feature of OSCC is microenvironmental oxygen depletion due to rapid growth of constituent tumor cells, which triggers hypoxia-associated signaling events and metabolic adaptations that influence subsequent tumor progression. Better understanding of leukocyte responses to tissue hypoxia and onco-metabolite expression under low-oxygen conditions will therefore be essential to develop more effective methods of diagnosing and treating patients with OSCC. This review assesses recent literature on metabolic reprogramming, redox homeostasis, and associated signaling pathways that mediate crosstalk of OSCC with immune cells in the hypoxic tumor microenvironment. The likely functional consequences of this metabolic interface between oxygen-starved OSCC and infiltrating leukocytes are also discussed. The hypoxic microenvironment of OSCC modifies redox signaling and alters the metabolic profile of tumor-infiltrating immune cells. Improved understanding of heterotypic interactions between host leukocytes, tumor cells, and hypoxia-induced onco-metabolites will inform the development of novel theranostic strategies for OSCC.

Systematic Investigation of Biocompatible Cationic Polymeric Nucleic Acid Carriers for Immunotherapy of Hepatocellular Carcinoma

“…Liu and co-authors have developed a novel drug vector to inhibit glycolysis of cancer cells and mitigate the immunosuppressive microenvironment [ 206 ]. Chaudhary and co-authors have reviewed recent literatures on metabolic reprogramming and associated signaling pathways that mediate crosstalk of tumor with immune cells [ 207 ]. As shown in Figure 6 , they have provided a scheme as to metabolic crosstalk of tumor and immune cells in tumor microenvironment.…”

“… Metabolic crosstalk of tumor and immune cells in the tumor microenvironment ([ 207 ] Front. Oral Health 2020 , 1 , 585710).…”