TY - JOUR
T1 - Hypoxia Reduction Sensitizes Refractory Cancers to Immunotherapy
AU - Jayaprakash, Priyamvada
AU - Vignali, Paolo Dario Angelo
AU - Delgoffe, Greg M.
AU - Curran, Michael A.
N1 - Publisher Copyright:
© 2022 Annual Reviews Inc.. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Hypoxia
KW - Immune resistance
KW - Immunotherapy
KW - Oxidative phosphorylation
KW - Tumor microenvironment
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U2 - 10.1146/annurev-med-060619-022830
DO - 10.1146/annurev-med-060619-022830
M3 - Review article
C2 - 34699264
AN - SCOPUS:85120421206
SN - 0066-4219
VL - 73
SP - 251
EP - 265
JO - Annual Review of Medicine
JF - Annual Review of Medicine
ER -