The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

Qin, Weiting; Hu, Li-Peng; Zhang, Xueli; Jiang, Shu-Heng; Li, Jun; Zhang, Zhigang; Wang, Xu

doi:10.3389/fimmu.2019.02298

Cited by 291 publications

(259 citation statements)

References 187 publications

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“…Another well-known mechanism of primary resistance to immunotherapy is the upregulation of immune checkpoint molecules on tumor cells. One such immunosuppressive molecule, programmed death-ligand 1 (PD-L1), binds to the inhibitory programmed death 1 (PD-1) receptor on T cells and inhibits their activation and cytotoxic functions [92]. Interestingly, PD-L1 is now considered to be a target gene of HIF-1α and HIF-2α, indicating a crucial role of intratumoral hypoxia in the regulation of this immunosuppressive ligand [93][94][95][96].…”

Section: Hypoxia-mediated Primary Resistancementioning

confidence: 99%

Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Vito

El-Sayes

Mossman

2020

Cells

169

153

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The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways.

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Section: Hypoxia-mediated Primary Resistancementioning

confidence: 99%

Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Vito

El-Sayes

Mossman

2020

Cells

169

153

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“…It is suggested that an importance function of IL-10 in ATL may be inhibitory activities on macrophages and Th1and also as a means of escaping host defenses. It has been implicated that the negative regulatory programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway has an important role in the induction of CTL exhaustion during chronic viral infection and tumor (30)(31)(32). According to previous studies, suppression of immune responses and CTLs exhaustion lead to progression of disease to ATLL (33).…”

Section: Discussionmentioning

confidence: 99%

Which One of the Human Immune Genes are more Involved in Against HTLV-1 Infection?

Keikha

Ali‐Hassanzadeh

Bagheri

2020

Preprint

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Background: Human T-lymphotropic virus type 1 (HTLV-1) is a main member of type C retrovirus. This virus was first isolated from cutaneous T-cell lymphoma cases. Among all infected individuals, only 5% of cases progress to acute form, and 4% of them to chronic form. Nevertheless, about 90% of patients remain asymptomatic. Adult T cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are accounted as acute and chronic forms of disease respectively.Methods: The gene expression profile of CD4+ T cells in four groups, healthy donors, asymptomatic HTLV-1 carriers (ACs), HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis), and ATLL (Adult T-cell leukemia/lymphoma) based on GPL9686 platform was evaluated. Results: According to Gene enrichment analysis, it was determined that hub genes in present study are able effect on various pathways such as apoptosis, proliferation and T cell activation, Ras signaling pathway, integrin signaling pathway, P53 signaling pathway, CCKR, TLR, FGF, DNA Damage, MAPK signaling, integrated cancer, Caspase, NF-κB, BCL-2 family, survival complex, breast cancer, Pancreatic cancer.Conclusions: Overall, based on scientific results in the present study, it seems the immune system via stimulation of biological processes such as cell survival, proliferation, CTLs exhaustion, and apoptosis concomitant, caused immortalization of HTLV-1 infected CD4+ T cells.

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“…PDL1 encoding PD-L1. Considering, the PD-L1-programmed cell death protein 1 axis plays a critical role in the induction of Treg cells as well as being involved in immune evasion, 73 the observation that helminth PCF did not upregulate PDL1 gene expression suggests that other immune evasive mechanisms might be employed by A. suum.…”

Section: Discussionmentioning

confidence: 99%

Body fluid from the parasitic worm Ascaris suum inhibits broad‐acting pro‐inflammatory programs in dendritic cells

et al. 2019

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Dendritic cells (DCs) are essential for generating T-cell-based immune responses through sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the resultant DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-c (IFN-c)-stimulated human monocytederived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid [helminth pseudocoelomic fluid (PCF)], the metabolites succinate and butyrate, and the type 2 cytokines thymic stromal lymphopoietin and interleukin-25. Our data show that helminth PCF and butyrate treatment suppress the T helper type 1 (Th1)inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS + IFN-c-matured DCs by down-regulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in Toll-like receptor 4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, and transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were up-regulated. Collectively, our results further understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.

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The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

Cited by 291 publications

References 187 publications

Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Which One of the Human Immune Genes are more Involved in Against HTLV-1 Infection?

Body fluid from the parasitic worm Ascaris suum inhibits broad‐acting pro‐inflammatory programs in dendritic cells

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