Hypoxia Reduction Sensitizes Refractory Cancers to Immunotherapy

In order to fuel their relentless expansion, cancers must expand their vasculature to augment delivery of oxygen and essential nutrients. The disordered web of irregular vessels that results, however, leaves gaps in oxygen delivery that foster tumor hypoxia. At the same time, tumor cells increase their oxidative metabolism to cope with the energetic demands of proliferation, which further worsens hypoxia due to heightened oxygen consumption. In these hypoxic, nutrient-deprived environments, tumors and suppressive stroma evolve to flourish while antitumor immunity collapses due to a combination of energetic deprivation, toxic metabolites, acidification, and other suppressive signals. Reversal of cancer hypoxia thus has the potential to increase the survival and effector function of tumor-infiltrating T cells, as well as to resensitize tumors to immunotherapy. Early clinical trials combining hypoxia reduction with immune checkpoint blockade have shown promising results in treating patients with advanced, metastatic, and therapeutically refractory cancers.

Automated summary

To support their growth, cancers need to increase their blood vessel density for oxygen and nutrient delivery. However, this irregular vasculature results in insufficient oxygen supply, leading to tumor hypoxia. In hypoxic and nutrient-deprived conditions, tumors and suppressive stroma thrive while antitumor immunity weakens. Reversing cancer hypoxia has the potential to improve the survival and function of tumor-infiltrating T cells and make tumors responsive to immunotherapy.