Cellular & Molecular Immunology - Metabolic rewiring controlled by HIF-1α tunes IgA-producing B-cell differentiation and intestinal inflammation

Yang et al. report that HIF-1α acts as a main driver of tumor resistance to cuproptosis under hypoxia. Mechanistically, they reveal that HIF-1α can repress DLAT expression and promote MT2A to sequeste...

A deeper understanding of how tissue-localized immune cells arise and function is critical for developing mucosal vaccines. Currently, there are no mu…

Clear cell renal cell carcinoma (ccRCC) is largely driven by the transcription factor hypoxia-inducible factor 2α (HIF-2α)1. Here we show that monotherapy with casdatifan—an orally bioavailable, potent and selective HIF-2α inhibitor2—produces meaningful, durable antitumour activity with manageable safety in individuals with refractory metastatic ccRCC. Dose-expansion data from the ARC-20 study ( NCT05536141 ) are presented, including for the 100 mg once daily (QD) cohort (n = 32) and the total cohort (n = 127). Treatment discontinuation from casdatifan-related adverse events was infrequent (3%), and class-effect toxicities included anaemia and hypoxia. The confirmed objective response rates (ORRs) were 35% (95% confidence intervals (CI) = 19–55%; 100 mg QD) and 31% (95% CI = 23–40%; total); median progression-free survival (PFS) was not estimable (95% CI = 5.7–not estimable; 100 mg QD) and 12.2 months (9.4–20.6; total). Greater maximal reductions in serum

Tertiary lymphoid structures are critical components of tissue immunity, necessitating better understanding of their organization and immune functions. De Lima et al. investigate the spatial and temporal distribution of lung HIF-1α-active CD4⁺ T cells. They show that HIF-1α activity sustains lung-resident CD4+ T cells that organize an IL-21-dependent immune network, integrating local protection during infection and cancer.

Lactate produced by dendritic cells (DCs) suppresses T-cell-mediated autoimmunity through a mechanism in which lactate activates HIF-1α–NDUFA4L2 signalling in DCs and thereby limits DC-mediated pro...

Li et al. identify XZA-1 as a small-molecule activator of HADH that increases acetoacetyl-CoA, inducing CBX4 K106 acetoacetylation. This modification suppresses CBX4 SUMO E3 ligase activity, reduces HIF-1α SUMOylation, and attenuates its transcriptional activity.

Deng et al. demonstrate that, under hypoxic conditions, resting cytoplasmic IRF3 interacts with HIF-1α and HIF-2α, which leads to the retention of HIF-α proteins in the cytoplasm. Consequently, IRF3 inhibits the transcription factor function of HIF-α and attenuates hypoxia signaling.

Angiogenesis, driven by VEGF and HIF-1α, forms blood vessels in healing, cancer, and ischemia—balancing pro- and anti-angiogenic signals shapes tumor growth and metastasis.

pVHL regulates alveolar macrophage phenotypical maturation and self-renewal. Priego et al. show that HIF-1α specifically drives a glycolytic switch and controls self-renewal along with HIF-2α, while HIF-2α specifically regulates lipid oxidation and surfactant clearance. This reveals how oxygen sensing shapes macrophage identity and adaptation to the alveolar niche.

Inflammatory hypoxia is induced by eosinophilic inflammation, while a decreased expression in the key hypoxic regulator, hypoxia-inducible transcripti…

Aims/hypothesis Diabetic kidney disease (DKD) features intrarenal inflammation, in which T cells play a part. Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor regulating cellular respo...

Read the full paper: HIF-1α-driven lactate from mesenchymal stem/stromal cells reprograms monocyte metabolism and suppresses autoimmune uveoretinitis

Tertiary lymphoid structures are critical components of tissue immunity, necessitating better understanding of their organization and immune functions. De Lima et al. investigate the spatial and tempo...