The impact of hypoxia on tumor-mediated bypassing anti-PD-(L)1 therapy

被引:21
|
作者
Mortezaee, Keywan [1 ]
Majidpoor, Jamal [2 ]
Kharazinejad, Ebrahim [3 ]
机构
[1] Kurdistan Univ Med Sci, Sch Med, Dept Anat, Sanandaj, Iran
[2] Gonabad Univ Med Sci, Infect Dis Res Ctr, Sch Med, Dept Anat, Gonabad, Iran
[3] Abadan Univ Med Sci, Fac Med, Dept Anat, Abadan, Iran
关键词
Hypoxia; Hypoxia inducible factor-1 (HIF-1); Resistance; Programmed death-ligand 1 (PD-L1); Programmed death-1 (PD-1); Immune checkpoint inhibitor (ICI); Heterogeneity; CD8; T-CELLS; PD-1; BLOCKADE; CANCER; MACROPHAGES; CHECKPOINT; B7-H1; IMMUNITY; SUBSETS; AGGRESSIVENESS; HETEROGENEITY;
D O I
10.1016/j.biopha.2023.114646
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Extending the durability of response is the current focus in cancer immunotherapy with immune checkpoint inhibitors (ICIs). However, factors like non-immunogenic tumor microenvironment (TME) along with aberrant angiogenesis and dysregulated metabolic systems are negative contributors. Hypoxia is a key TME condition and a critical promoter of tumor hallmarks. It acts on immune and non-immune cells within TME in order for promoting immune evasion and therapy resistance. Extreme hypoxia is a major promoter of resistance to the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Hypoxia inducible factor-1 (HIF-1) acts as a key mediator of hypoxia and a critical promoter of resistance to the anti-PD-(L)1. Targeting hypoxia or HIF-1 can thus be an effective strategy for reinvigoration of cellular immunity against cancer. Among various strategies presented so far, the key focus is over vascular normalization, which is an approach highly effective for reducing the rate of hypoxia, increasing drug delivery into the tumor area, and boosting the efficacy of anti-PD-(L)1.
引用
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页数:11
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