TY - JOUR
T1 - Hypoxia-driven immunosuppressive metabolites in the tumor microenvironment
T2 - New approaches for combinational immunotherapy
AU - Li, Yiliang
AU - Patel, Sapna Pradyuman
AU - Roszik, Jason
AU - Qin, Yong
N1 - Publisher Copyright:
© 2018 Li, Patel, Roszik and Qin.
PY - 2018/7/16
Y1 - 2018/7/16
N2 - Hypoxia is not only a prominent contributor to the heterogeneity of solid tumors but also a crucial stressor in the microenvironment to drive adaptations for tumors to evade immunosurveillance. Herein, we discuss the potential role of hypoxia within the microenvironment contributing to immune resistance and immune suppression of tumor cells. We outline recent discoveries of hypoxia-driven adaptive mechanisms that diminish immune cell response via skewing the expression of important immune checkpoint molecules (e.g., cluster of differentiation 47, programmed death ligand 1, and human leukocyte antigen G), altered metabolism and metabolites, and pH regulation. Importantly, inhibition of hypoxic stress-relevant pathways can collectively enhance T-cell-mediated tumor cell killing. Furthermore, we discuss how manipulation of hypoxia stress may pose a promising new strategy for a combinational therapeutic intervention to enhance immunotherapy of solid tumors.
AB - Hypoxia is not only a prominent contributor to the heterogeneity of solid tumors but also a crucial stressor in the microenvironment to drive adaptations for tumors to evade immunosurveillance. Herein, we discuss the potential role of hypoxia within the microenvironment contributing to immune resistance and immune suppression of tumor cells. We outline recent discoveries of hypoxia-driven adaptive mechanisms that diminish immune cell response via skewing the expression of important immune checkpoint molecules (e.g., cluster of differentiation 47, programmed death ligand 1, and human leukocyte antigen G), altered metabolism and metabolites, and pH regulation. Importantly, inhibition of hypoxic stress-relevant pathways can collectively enhance T-cell-mediated tumor cell killing. Furthermore, we discuss how manipulation of hypoxia stress may pose a promising new strategy for a combinational therapeutic intervention to enhance immunotherapy of solid tumors.
KW - Hypoxia
KW - Immunosuppression
KW - Immunotherapy
KW - Metabolism
KW - Microenvironment
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U2 - 10.3389/fimmu.2018.01591
DO - 10.3389/fimmu.2018.01591
M3 - Review article
C2 - 30061885
AN - SCOPUS:85050155706
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JUL
M1 - 1591
ER -