The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation

Fan, Zusen; Wu, Changyue; Chen, Miaomiao; Jiang, Yongying; Wu, Yuanyuan; Mao, Renfang; Fan, Yihui

doi:10.1016/j.apsb.2021.09.010

Cited by 50 publications

(29 citation statements)

References 116 publications

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“…Our results agree with these prior reports confirming integration in or near these genes. Our study identified additional non-recurrent, cancer-associated genes in or near integration sites in HPV+ OPSCC including TGFBR2 , FGFR2 [ 20 ], PD-L2 [ 57 ], TRAF3 [ 26 ], BRCA1 , SPOP [ 58 ], and BCL-2 [ 59 ] Our results bolster prior reports that modulation of the function of genes near HPV integration sites is key in the oncogenesis if OPSCC [ 7 ]. As other studies investigating HPV integration in UCSCC have found, we noted HPV16 integration near NR4A2 , MYC [ 60 ], LRP1B [ 61 , 62 , 63 ], and MACROD2 [ 54 ].…”

Section: Discussionsupporting

confidence: 84%

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

Schrank

Kim

Rehmani

et al. 2022

Cancers

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Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC.

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Section: Discussionsupporting

confidence: 84%

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

Schrank

Kim

Rehmani

et al. 2022

Cancers

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“…In tumor cells, transcriptional expression of PD-L1 is often not directly related to protein expression due to stabilizing post-translational modifications, such as N-glycosylation and phosphorylation [ 49 , 50 ]. Moreover, it can be accumulated in vesicles, such as exosomes [ 5 ] or secretory lysosomes, as demonstrated for LCLs [ 37 ], where we observed cytoplasmic accumulation.…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

et al. 2023

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Epstein–Barr virus (EBV) infects 95% of the world’s population and persists latently in the body. It immortalizes B-cells and is associated with lymphomas. LCLs (lymphoblastoid cell lines, EBV latency III B-cells) inhibit anti-tumoral T-cell response following PD-L1 overexpression (programmed death-ligand 1 immune checkpoint). Many cancer cells, including some DLBCLs (diffuse large B-cell lymphomas), also overexpress PD-L1. Immunotherapies are based on inhibition of PD-L1/PD-1 interactions but present some dose-dependent toxicities. We aim to find new strategies to improve their efficiency by decreasing PD-L1 expression. Fucoidan, a polysaccharide extracted from brown seaweed, exhibits immunomodulatory and anti-tumor activities depending on its polymerization degree, but data are scarce on lymphoma cells or immune checkpoints. LCLs and DLBCLs cells were treated with native fucoidan (Fucus vesiculosus) or original very-low-molecular-weight fucoidan formulas (vLMW-F). We observed cell proliferation decrease and apoptosis induction increase with vLMW-F and no toxicity on normal B- and T-cells. We highlighted a decrease in transcriptional and PD-L1 surface expression, even more efficient for vLMW than native fucoidan. This can be explained by actin network alteration, suggesting lower fusion of secretory vesicles carrying PD-L1 with the plasma membrane. We propose vLMW-F as potential adjuvants to immunotherapy due to their anti-proliferative and proapoptotic effects and ability to decrease PD-L1 membrane expression.

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“…Existing literature suggests that IL1RN is closely related to tumor immunity and tumor metabolism, of which further studies are needed to investigate its value in the prognosis of immune infiltration. According to our study, a strong correlation was shown between IL1RN and CD274, which is well-known as PD-L1 [ 47 ]. A brunch of evidences could confirm the role of PD1/PDL1, an essential component of immune checkpoints, in regulating TIL function [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…According to our study, a strong correlation was shown between IL1RN and CD274, which is well-known as PD-L1 [ 47 ]. A brunch of evidences could confirm the role of PD1/PDL1, an essential component of immune checkpoints, in regulating TIL function [ 47 ]. CD274 participates widely in the resistance of various cancers to treatment, such as chemotherapy and targeted therapies as an important immunosuppressive factor [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

IL1RN and PRRX1 as a Prognostic Biomarker Correlated with Immune Infiltrates in Colorectal Cancer: Evidence from Bioinformatic Analysis

Wang

Huang

Zhou

et al. 2022

International Journal of Genomics

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The extensive morbidity of colorectal cancer (CRC) and the inferior prognosis of terminal CRC urgently call for reliable prognostic biomarkers. For this, we identified 704 differentially expressed genes (DEGs) by intersecting three datasets, GSE41328, GSE37364, and GSE15960 from Gene Expression Omnibus database, to maximize the accuracy of the results. Preliminary analysis of the DEGs was then performed using online gene analysis datasets, such as DAVID, UCSC Cancer Genome Browser, CBioPortal, STRING, and UCSC Cancer Genome Browser. Cytoscape was utilized to visualize the protein perception interaction network of DEGs, and the bubble map of GO and KEGG enrichment function was demonstrated using the R package. The Molecular Complex Detection (MCODE), Biological Network Gene Oncology (BiNGO) plug-in in Cytoscape, was applied to further screen the DEGs to obtain 15 seed genes, which were IL1RN, GALNT12, ADH6, SCN7A, CXCL1, FGF18, SOX9, ACACB, PRRX1, MZB1, SLC22A3, CNNM4, LY6E, IFITM2, and GDPD3. Among them, IL1RN, ADH6, SCN7A, ACACB, MZB1, and GDPD3 exhibited statistically significant survival differences, whereas limited studies were conducted in CRC. Based on the enrichment results of the “Gene Ontology“(GO) and “Kyoto Encyclopedia of Genes and genomes “(KEGG) as well as documented findings of key genes, we further emphasized the potential of IL1RN and PRRX1 as markers of immune infiltrates in CRC and confirmed our hypothesis by compiling data from the UALCAN, Tumor Immune Estimation Resource, and TISIDB databases for these two genes. The above-mentioned genes might offer a valuable insight into the diagnosis, immunotherapeutic targets, and prognosis of CRC.

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The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation

Cited by 50 publications

References 116 publications

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

IL1RN and PRRX1 as a Prognostic Biomarker Correlated with Immune Infiltrates in Colorectal Cancer: Evidence from Bioinformatic Analysis

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