PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation

By M. Noman, G. Desantis, B. Janji, M. Hasmim, S. Karray, Philippe Dessen, V. Bronte, S. Chouaib. Journal of Experimental Medicine, 2014

1,918 citations recorded by the source corpus.

Hypoxia selectively up-regulates PD-L1 on myeloid-derived suppressor cells via HIF-1a, thus affecting T cell activation.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/dad078dcb463c50f1571acb3306b01954a153c29

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. V. Nizet
2. S. Shalapour
3. Richard J. Johnson
4. J. Pollard
5. M. Karin
6. Michael D. Buck
7. Yongqian Shu
8. Ke Wei

In Immunology

1. M. Karin
2. R. Noy
3. J. Pollard
4. S. Shalapour
5. Rakesh K. Jain
6. Michael D. Buck
7. D. Marvel
8. V. Nizet

Citations in the corpus

• HIF Transcription Factors, Inflammation, and Immunity (2014, background): “Myeloid-derived suppressor cells are another stromal component that can dampen antitumor immunity, and HIF-1a can modulate their function and differentiation into tumor-associated macrophages (Corzo et al., 2010) and their expression of the immune checkpoint ligand PD-L1 (Noman et al., 2014).”
• Metabolic Instruction of Immunity (2017, positive): “In addition to signals received from TIL IFN-γ (Noman et al., 2014), HIF-1α also induces the expression of the suppressive ligand PD-L1 in tumor cells, TAMs, and myeloid-derived suppressor cells (MDSCs), and this can lead to TIL suppression via PD-1 (Figure 1).”
• Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. (2016, background): “In addition, hypoxia-induced HIF-1α drives expression of the immune checkpoint protein PD-L1, which contributes to immune suppression and evasion (Noman et al., 2014).”
• Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. (2015, background): “A recent report demonstrated that HIF-1α bound to the promoter of programmed cell death ligand-1 (PD-L1) and upregulated its expression on myeloid cells (65).”
• Regulation of PD-L1: a novel role of pro-survival signalling in cancer. (2016, background): “Increased HIF-1 levels are associated with increased PD-L1 expression and cause down-regulation of T-Cell function[66-71], suggesting hypoxic environments, which leads to increased expression of HIF-1, can also result in immune suppression in addition to promoting cell proliferation and blocking apo”
• Role of hypoxia in cancer therapy by regulating the tumor microenvironment (2019, background): “Myeloid-derived suppressor cells (MDSCs) can directly promote immune tolerance [58].”
• Immunity, inflammation, and cancer: an eternal fight between good and evil. (2015, positive): “TAMs can also express programmed death-1 ligand (PD- L1) upon activation of HIF-1α in hypoxic tumor regions, further inhibiting CTL activation (70).”