PD-1 and its ligands are important immune checkpoints in cancer

Dong, Yinan; Sun, Qian; Zhang, Xinwei

doi:10.18632/oncotarget.13895

Cited by 278 publications

(233 citation statements)

References 140 publications

(192 reference statements)

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“…Among them, PDCD8 and PDCD9 are officially known as AIFM1 and MRPS30, respectively. PDCD1, often known as PD-1, is the member that has been most extensively studied and shown to negatively regulate T cell responses, in collaboration with its two ligands, PD-L1 and PD-L2 (51)(52)(53). In addition to PDCD5, other programmed cell death proteins are also known to play important roles in apoptosis and/or cell cycle progression (54)(55)(56)(57), and are also dysregulated in many types of human cancers (13,16,(58)(59)(60)(61)(62)(63).…”

Section: Discussionmentioning

confidence: 99%

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

Hong-xin

Wang

et al. 2017

Oncol Lett

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Abstract. Programmed cell death (PDCD)5 is cloned from human leukemia cell line TF-1. PDCD5 is one of the members of the programmed cell death protein family that is frequently involved in tumor growth and apoptosis. To investigate the molecular and cellular functions of PDCD5, the present study established a PDCD5 stably overexpressing A431 cell line and examined the role of PDCD5 in cell proliferation, cell cycle progression and apoptosis. The data demonstrated that overexpression of PDCD5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis in A431 cells. The expression profiles of certain key regulators of these cellular events were further investigated, including P53, B cell lymphoma (BCL)-2, BCL-2 associated X protein (BAX) and caspase (CASP)3. The data demonstrated that at the transcript and protein levels, P53, BAX and CASP3 were all upregulated in the PDCD5 stably overexpressing A431 cells whereas BCL-2 was downregulated, indicating that PDCD5 acts as an important upstream regulator of P53, BCL-2, BAX and CASP3. The data suggest that PDCD5 regulates cell proliferation, cell cycle progression and apoptosis in A431 cells. PDCD5 may be a novel tumor suppressor gene, and may be potentially used for cancer treatment in the future.

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Section: Discussionmentioning

confidence: 99%

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

Hong-xin

Wang

et al. 2017

Oncol Lett

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“…Programmed death 1 (PD-1), also known as cluster of differentiation (CD)279, is an immune receptor belonging to the immunoglobulin superfamily (5,6). PD-1 is expressed on several immune cells, particularly activated T cells, B cells and myeloid cells, to modulate their activation or inhibition (6).…”

Section: Introductionmentioning

confidence: 99%

“…PD-1 has two ligands, programmed death ligand 1 (PD-L1), also known as B7 homolog 1 or CD274, and PD-L2 (B7-DC or CD273). PD-L2 is expressed predominantly on macrophages and dendritic cells, whereas PD-L1 is expressed on tumor cells and other immune cells (5,6). It was demonstrated that the inhibitory effect of PD-1 is accomplished through a mechanism of providing immune escape for tumor cells by inactivating cytotoxic T cells or inhibiting tumor cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen

et al. 2017

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Abstract.Interaction between the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) contributes to tumor cell resistance to chemotherapeutic agents. PD-L1 is expressed in the cells of diffuse large B-cell lymphoma (DLBCL), one common type of malignant non-Hodgkin lymphomas. However, little is known about how the PD-1/PD-L1 pathway functions in the pathogenesis of DLBCL. Therefore, the present study investigated whether and how the PD-1/PD-L1 axis is involved in regulating the sensitivity of CRL2631, a DLBCL cell line, to the CHOP (Cyclophosphamide, Hydroxydaunorubicin/adriamycin, Oncovin/vincristine and Prednisone) chemotherapeutic regimen. CHOP treatment significantly decreased cell survival rate and increased apoptosis in CRL2631 cells. The application of recombinant human PD-1 (rPD-1) significantly decreased the cytotoxic effects of the CHOP regimen in CRL2631 cells, but not in the CRL2631 cells with PD-L1 deficiency. In the CRL2631 cells, rPD-1 enhanced the activity of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt1) pathway. However, the activity level of the PI3K/Akt1 pathway was decreased in CHOP-treated CRL2631 cells. The selective PI3K inhibitor BKM120 significantly increased CHOP-induced apoptosis, but this effect was abolished by rPD-1 and aggravated by PD-L1 knockdown. In CHOP-treated PD-L1 knockdown cells, the increased apoptosis was markedly inhibited by the overexpression of constitutively active Akt1. Overall, the results demonstrate that the over-activated PD-1/PD-L1 axis is associated with chemotherapeutic resistance of DLBCL cells to the CHOP regimen, potentially through a PI3K-dependent mechanism.

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“…Here, the α‐CD19 synNotch receptor, when stimulated, induced the expression of [PD‐L1‐T2A‐IL‐10] . As the main ligand for PD‐1, PD‐L1 induces a co‐inhibitory signal in activated T‐cells and also stimulates cytokine IL‐10 production, further reducing the immune response …”

Section: Adoptive T‐cell Anti‐cancer Immunotherapymentioning

confidence: 99%

“Therapeutic applications of the ‘NPGP’ family of viral 2As”

Luke

Ryan

2018

Reviews in Medical Virology

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Oligopeptide "2A" and "2A-like" sequences ("2As"; 18-25aa) are found in a range of RNA virus genomes controlling protein biogenesis through "recoding" of the host-cell translational apparatus. Insertion of multiple 2As within a single open reading frame (ORF) produces multiple proteins; hence, 2As have been used in a very wide range of biotechnological and biomedical applications. During translation, these 2A peptide sequences mediate a eukaryote-specific, self-"cleaving" event, termed "ribosome skipping" with very high efficiency. A particular advantage of using 2As is the ability to simultaneously translate a number of proteins at an equal level in all eukaryotic systems although, naturally, final steady-state levels depend upon other factors-notably protein stability. By contrast, the use of internal ribosome entry site elements for co-expression results in an unbalanced expression due to the relative inefficiency of internal initiation. For example, a 1:1 ratio is of particular importance for the biosynthesis of the heavy-chain and light-chain components of antibodies: highly valuable as therapeutic proteins. Furthermore, each component of these "artificial polyprotein" systems can be independently targeted to different sub-cellular sites. The potential of this system was vividly demonstrated by concatenating multiple gene sequences, linked via 2A sequences, into a single, long, ORF-a polycistronic construct. Here, ORFs comprising the biosynthetic pathways for violacein (five gene sequences) and β-carotene (four gene sequences) were concatenated into a single cistron such that all components were co-expressed in the yeast Pichia pastoris. In this review, we provide useful information on 2As to serve as a guide for future utilities of this co-expression technology in basic research, biotechnology, and clinical applications.

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PD-1 and its ligands are important immune checkpoints in cancer

Cited by 278 publications

References 140 publications

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen

“Therapeutic applications of the ‘NPGP’ family of viral 2As”

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