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

Abstract

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

Myeloid‑derived suppressor cells in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease

“…Hypoxia dramatically and significantly increased the percentage of PD -L1 + MDSCs isolated from the spleen in B16 -F10 and LLC tumor -bearing mice. 38 Similar results were reported by Corzo et al 39 Hypoxia via HIF -1α dramatically alters the function of MDSCs in the tumor microenvironment and redirects their differentiation toward tumor -associated macrophages, hence providing a link between different MDSCs in the tumor microenvironment. We did not identify any study concerning the relationship of hypoxia and MDSCs in humans, especially in patients with COPD.…”

Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment

“…This ligand has been described to be expressed on MDSCs and tumor cells 20,21 and to induce T cell anergy by binding to its receptor PD-1. 22,23 In addition, we sorted recombined and non-recombined MDSCs from tumor bearing Cre-reporter mice (n D 2) and analyzed the expression of ARG-1, TGF-b and inducible nitric oxide synthase (iNOS) that play a key role in the MDSCmediated immunosuppression during the tumor progression. 20,24 The data revealed an upregulation of the expression of ARG-1 and TGF-b (to a lesser extent), suggesting the stimulation of MDSC immunosuppressive functions (Fig.…”

Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK

“…S7). Other studies have reported that anti-PD-L1 treatment alone is insufficient to alter MDSC arginase activity, expression of Nos-2 or NO production (25). Only by combining anti-PD-L1 with anti-CTLA4 mAb and two epigenetic-modulating drugs were MDSC's numbers reduced (26).…”