Hypoxia is a hallmark of glioblastoma multiforme (GBM), the most aggressive cancer of the central nervous system, and is associated with multiple aspects of tumor pathogenesis. For example, hypoxia induces resistance to conventional cancer therapies and inhibits antitumor immune responses. Thus, targeting hypoxia is an attractive strategy for GBM therapy. However, traditional studies on hypoxia have largely excluded the immune system. Recently, the critical role of the immune system in the defense against multiple tumors has become apparent, leading to the development of effective immunotherapies targeting numerous cancer types. Critically, however, GBM is classified as a “cold tumor” due to poor immune responses. Thus, to improve GBM responsiveness against immunotherapies, an improved understanding of both immune function in GBM and the role of hypoxia in mediating immune responses within the GBM microenvironment is needed. In this review, we discuss the role of hypoxia in GBM from a clinical, pathological, and immunological perspective.

Infiltrating tumor-associated macrophages (TAM) are known to impede immunotherapy against glioblastoma (GBM), however, TAMs are heterogeneous, and there are no clear markers to distinguish immunosuppressive and potentially immune-activating populations. Here we identify a subset of CD169⁺ macrophages promoting an anti-tumoral microenvironment in GBM. Using single-cell transcriptome analysis, we find that CD169⁺ macrophages in human and mouse gliomas produce pro-inflammatory chemokines, leading to the accumulation of T cells and NK cells. CD169 expression on macrophages facilitates phagocytosis of apoptotic glioma cells and hence tumor-specific T cell responses. Depletion of CD169⁺ macrophages leads to functionally impaired antitumor lymphocytes and poorer survival of glioma-bearing mice. We show that NK-cell-derived IFN-γ is critical for the accumulation of blood monocyte-derived CD169⁺ macrophages in gliomas. Our work thus identifies a well-distinguished TAM subset promoting antitumor immunity against GBM, and identifies key factors that might shift the balance from immunosuppressive to anti-tumor TAM.

The novel coronavirus, SARS-CoV-2, which causes COVID-19, has resulted in a pandemic with millions of deaths. To eradicate SARS-CoV-2 and prevent further infections, many vaccine candidates have been developed. These vaccines include not only traditional subunit vaccines and attenuated or inactivated viral vaccines but also nucleic acid and viral vector vaccines. In contrast to the diversity in the platform technology, the delivery of vaccines is limited to intramuscular vaccination. Although intramuscular vaccination is safe and effective, mucosal vaccination could improve the local immune responses that block the spread of pathogens. However, a lack of understanding of mucosal immunity combined with the urgent need for a COVID-19 vaccine has resulted in only intramuscular vaccinations. In this review, we summarize the history of vaccines, current progress in COVID-19 vaccine technology, and the status of intranasal COVID-19 vaccines. Future research should determine the most effective route for vaccine delivery based on the platform and determine the mechanisms that underlie the efficacy of different delivery routes.

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections in infants. Macroautophagy/autophagy is a catalytic metabolic process required for cellular homeostasis. Although intracellular metabolism is important for immune responses in dendritic cells, the link between autophagy and immunometabolism remains unknown. Here, we show that the autophagy-related protein ATG5 regulates immunometabolism. Atg5-deficient mouse dendritic cells showed increased CD8A⁺ T-cell response and increased secretion of proinflammatory cytokines upon RSV infection. Transcriptome analysis showed that Atg5 deficiency alters the expression of metabolism-related genes. Atg5-deficient dendritic cells also showed increased activation of glycolysis and the AKT-MTOR-RPS6KB pathway and decreased mitochondrial activity, all of which are cellular signatures for metabolic activation. These cells also showed elevated CD8A⁺ T-cell priming and surface major histocompatibility complex (MHC) class I expression. Our results suggested that ATG5 regulated host immune responses by modulating dendritic cell metabolism. These findings may help develop potential antiviral therapies that alter host immunity by regulating autophagy and immunometabolism.

Influenza is an infectious respiratory illness caused by the influenza virus. Though vaccines against influenza exist, they have limited efficacy. To additionally develop effective treatments, there is a need to study the mechanisms of host defenses from influenza viral infections. To date, the mechanism by which interleukin (IL)-33 modulates the antiviral immune response post-influenza infection is unclear. In this study, we demonstrate that exogenous IL-33 enhanced antiviral protection against influenza virus infection. Exogenous IL-33 induced the recruitment of dendritic cells, increased the secretion of pro-inflammatory cytokine IL-12, and promoted cytotoxic T-cell responses in the local microenvironment. Thus, our findings suggest a role of exogenous IL-33 in the antiviral immune response against influenza infection.

The purpose of this study is to investigate the impact of a high-salt diet (HSD), which is commonly found in Western countries, on the progression of glioma. Our research shows that the alterations in gut microbiota caused by an HSD facilitated the development of glioma. Mice fed an HSD have elevated levels of intestinal propionate, which accelerated the growth of glioma cells. We also find that propionate supplementation enhanced the response of glioma cells to low oxygen levels. Moreover, we identify a link between TGF-β signaling, response to low oxygen levels, and invasion-related pathways. Propionate treatment increases the expression of HIF-1α, leading to an increase in TGF-β1 production. Additionally, propionate treatment promotes glioma cell invasion through TGF-β signaling. Our findings suggest that an HSD-induced increase in propionate plays a crucial role in glioma progression by facilitating invasion through the hypoxic response and TGF-β signaling pathways, thereby establishing a significant connection between gut microbiota and the progression of glioma.