Inhibition of OXPHOS induces metabolic rewiring and reduces hypoxia in murine tumor models.

Introduction: Tumor hypoxia is a feature of many solid malignancies and is known to cause radio resistance. In recent years it has become clear that hypoxic tumor regions also foster an immunosuppressive phenotype and are involved in immunotherapy resistance. It has been proposed that reducing the tumors' oxygen consumption will result in an increased oxygen concentration in the tissue and improve radio- and immunotherapy efficacy.

MHC-I and PD-L1 Expression is Associated with Decreased Tumor Outgrowth and is Radiotherapy-inducible in the Murine Head and Neck Squamous Cell Carcinoma Model MOC1.

Introduction: Combined radiotherapy and immune checkpoint inhibition is a potential treatment option for head and neck squamous cell carcinoma (HNSCC). Immunocompetent mouse models can help to successfully develop radio- immunotherapy combinations and to increase our understanding of the effects of radiotherapy on the tumor microenvironment for future clinical translation. Therefore, the aim of this study was to develop a homogeneous, reproducible HNSCC model originating from the Mouse Oral Cancer 1 (MOC1) HNSCC cell line, and to explore the radiotherapy-induced changes in its tumor microenvironment, using flow cytometry and PD-L1 microSPECT/CT imaging.

Towards effective CAIX-targeted radionuclide and checkpoint inhibition combination therapy for advanced clear cell renal cell carcinoma.

Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity.

Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging.

Background: Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities.

Quantitative Imaging of Hypoxic CAIX-Positive Tumor Areas with Low Immune Cell Infiltration in Syngeneic Mouse Tumor Models.

Limited diffusion of oxygen in combination with increased oxygen consumption leads to chronic hypoxia in most solid malignancies. This scarcity of oxygen is known to induce radioresistance and leads to an immunosuppressive microenvironment. Carbonic anhydrase IX (CAIX) is an enzyme functioning as a catalyzer for acid export in hypoxic cells and is an endogenous biomarker for chronic hypoxia.

Letter to the editor: Hypoxia kinetics and histology in combined radiotherapy and oxidative phosphorylation inhibition effects on antitumor immunity.

In response to the recent paper by Chen investigating the triple combination of oxidative phosphorylation inhibition, immunotherapy and radiotherapy, we would like to stress that after irradiation, a strong reduction in hypoxia (within 24 hours) can be followed by a strong increase (several days). This is especially the case with larger fraction sizes of radiation therapy, which are often applied in combination with immunotherapy, and is likely to be tumor dependent. All together this may strongly affect the synergistic effect of such a triple combination therapy.

Targeting Oxidative Phosphorylation to Increase the Efficacy of Radio- and Immune-Combination Therapy.

As tumors grow, they upregulate glycolytic and oxidative metabolism to support their increased and altered energetic demands. These metabolic changes have major effects on the tumor microenvironment. One of the properties leading to this aberrant metabolism is hypoxia, which occurs when tumors outgrow their often-chaotic vasculature.

Serial propagation in water-in-oil emulsions selects for Saccharomyces cerevisiae strains with a reduced cell size or an increased biomass yield on glucose.

In S. cerevisiae and many other micro-organisms an increase in metabolic efficiency (i.e.