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2018 ; 9
(ä): 1591
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Hypoxia-Driven Immunosuppressive Metabolites in the Tumor Microenvironment: New
Approaches for Combinational Immunotherapy
#MMPMID30061885
Li Y
; Patel SP
; Roszik J
; Qin Y
Front Immunol
2018[]; 9
(ä): 1591
PMID30061885
show ga
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.