Academic Journal
View in EDS

A novel TLR4 binding protein, 40S ribosomal protein S3, has potential utility as an adjuvant in a dendritic cell-based vaccine

Bibliographic Details
Title: A novel TLR4 binding protein, 40S ribosomal protein S3, has potential utility as an adjuvant in a dendritic cell-based vaccine
Authors: Hyun Jin Park, Gun-Young Jang, Young Seob Kim, Jung Hwa Park, Sung Eun Lee, Manh-Cuong Vo, Je-Jung Lee, Hee Dong Han, In Duk Jung, Tae Heung Kang, Yeong-Min Park
Source: Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-13 (2019)
Publisher Information: BMJ Publishing Group, 2019.
Publication Year: 2019
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Dendritic cell (DC), Toll-like receptor 4 (TLR4), DC based vaccine, 40S ribosomal protein S3 (RPS3), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Abstract Background Dendritic cells (DCs) are professional antigen presenting cells (APCs), which can activate antigen-specific CD8+ T cell immunity, resulting in tumor clearance. Immature DCs are usually stimulated by various adjuvants through their immune receptors. Among them, Toll-like receptor 4 (TLR4) has an important role in activating DCs to cause their maturation. In fact, TLR4 is well-known to induce innate and adaptive immune responses against various external microbial or internal damage associated molecular patterns (DAMP). LPS is widely regarded as a strong stimulator of TLR4 signaling. However, LPS is inappropriate for use in humans since it is an endotoxin. Unfortunately, other TLR4 ligands such as HMGB1 or heat shock proteins have weak adjuvant effects. Therefore, there is a need to identify novel, biocompatible, strong, TLR4 ligands. Methods 40S ribosomal protein S3 (RPS3) was screened through pull-down assay using TLR4. BMDCs from wild type (WT) and TLR4 knock-out mice were treated by RPS3 to identify the activation and maturation of DCs. T cell generation including memory T cells, tumor prevention, and treatment experiments were performed with BMDCs based vaccination. Also, human DCs originated from patients were treated by RPS3 to confirm the activation and maturation of DCs. Results In this study, we identified 40S ribosomal protein S3 (RPS3) through a pull-down assay using a variety of human cancer cell-derived proteins that could bind to TLR4. RPS3 was released from tumor cells following treatment with an anticancer drug, and it was shown that the released RPS3 binds to TLR4. Recombinant RPS3 induced maturation and activation of DCs, and following pulsing with tumor specific antigens, these DCs could be used as a vaccine to significantly increase tumor specific CD8+IFN-γ+ T cells, and provide both tumor prevention and tumor treatment effects. The effect of RPS3 on DC maturation and its utility as a vaccine were shown to be dependent on TLR4 using TLR4 knockout mice. Conclusions This study therefore proved that human cancer cell-derived RPS3, a novel TLR4 ligand, has great potential as an adjuvant in tumor-specific antigen DC-based vaccines.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2051-1426
Relation: http://link.springer.com/article/10.1186/s40425-019-0539-7; https://doaj.org/toc/2051-1426
DOI: 10.1186/s40425-019-0539-7
Access URL: https://doaj.org/article/1cd143757e744b09a088290bbaa52a8e
Accession Number: edsdoj.1cd143757e744b09a088290bbaa52a8e
Database: Directory of Open Access Journals
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edsdoj&genre=article&issn=20511426&ISBN=&volume=7&issue=1&date=20190201&spage=1&pages=1-13&title=Journal for ImmunoTherapy of Cancer&atitle=A%20novel%20TLR4%20binding%20protein%2C%2040S%20ribosomal%20protein%20S3%2C%20has%20potential%20utility%20as%20an%20adjuvant%20in%20a%20dendritic%20cell-based%20vaccine&aulast=Hyun%20Jin%20Park&id=DOI:10.1186/s40425-019-0539-7
    Name: Full Text Finder (for New FTF UI) (s8985755)
    Category: fullText
    Text: Find It @ SCU Libraries
    MouseOverText: Find It @ SCU Libraries
  – Url: https://doaj.org/article/1cd143757e744b09a088290bbaa52a8e
    Name: EDS - DOAJ (s8985755)
    Category: fullText
    Text: View record from DOAJ
    MouseOverText: View record from DOAJ
Header DbId: edsdoj
DbLabel: Directory of Open Access Journals
An: edsdoj.1cd143757e744b09a088290bbaa52a8e
RelevancyScore: 918
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 917.677612304688
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: A novel TLR4 binding protein, 40S ribosomal protein S3, has potential utility as an adjuvant in a dendritic cell-based vaccine
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Hyun+Jin+Park%22">Hyun Jin Park</searchLink><br /><searchLink fieldCode="AR" term="%22Gun-Young+Jang%22">Gun-Young Jang</searchLink><br /><searchLink fieldCode="AR" term="%22Young+Seob+Kim%22">Young Seob Kim</searchLink><br /><searchLink fieldCode="AR" term="%22Jung+Hwa+Park%22">Jung Hwa Park</searchLink><br /><searchLink fieldCode="AR" term="%22Sung+Eun+Lee%22">Sung Eun Lee</searchLink><br /><searchLink fieldCode="AR" term="%22Manh-Cuong+Vo%22">Manh-Cuong Vo</searchLink><br /><searchLink fieldCode="AR" term="%22Je-Jung+Lee%22">Je-Jung Lee</searchLink><br /><searchLink fieldCode="AR" term="%22Hee+Dong+Han%22">Hee Dong Han</searchLink><br /><searchLink fieldCode="AR" term="%22In+Duk+Jung%22">In Duk Jung</searchLink><br /><searchLink fieldCode="AR" term="%22Tae+Heung+Kang%22">Tae Heung Kang</searchLink><br /><searchLink fieldCode="AR" term="%22Yeong-Min+Park%22">Yeong-Min Park</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-13 (2019)
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: BMJ Publishing Group, 2019.
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2019
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Dendritic+cell+%28DC%29%22">Dendritic cell (DC)</searchLink><br /><searchLink fieldCode="DE" term="%22Toll-like+receptor+4+%28TLR4%29%22">Toll-like receptor 4 (TLR4)</searchLink><br /><searchLink fieldCode="DE" term="%22DC+based+vaccine%22">DC based vaccine</searchLink><br /><searchLink fieldCode="DE" term="%2240S+ribosomal+protein+S3+%28RPS3%29%22">40S ribosomal protein S3 (RPS3)</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplasms%2E+Tumors%2E+Oncology%2E+Including+cancer+and+carcinogens%22">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</searchLink><br /><searchLink fieldCode="DE" term="%22RC254-282%22">RC254-282</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Abstract Background Dendritic cells (DCs) are professional antigen presenting cells (APCs), which can activate antigen-specific CD8+ T cell immunity, resulting in tumor clearance. Immature DCs are usually stimulated by various adjuvants through their immune receptors. Among them, Toll-like receptor 4 (TLR4) has an important role in activating DCs to cause their maturation. In fact, TLR4 is well-known to induce innate and adaptive immune responses against various external microbial or internal damage associated molecular patterns (DAMP). LPS is widely regarded as a strong stimulator of TLR4 signaling. However, LPS is inappropriate for use in humans since it is an endotoxin. Unfortunately, other TLR4 ligands such as HMGB1 or heat shock proteins have weak adjuvant effects. Therefore, there is a need to identify novel, biocompatible, strong, TLR4 ligands. Methods 40S ribosomal protein S3 (RPS3) was screened through pull-down assay using TLR4. BMDCs from wild type (WT) and TLR4 knock-out mice were treated by RPS3 to identify the activation and maturation of DCs. T cell generation including memory T cells, tumor prevention, and treatment experiments were performed with BMDCs based vaccination. Also, human DCs originated from patients were treated by RPS3 to confirm the activation and maturation of DCs. Results In this study, we identified 40S ribosomal protein S3 (RPS3) through a pull-down assay using a variety of human cancer cell-derived proteins that could bind to TLR4. RPS3 was released from tumor cells following treatment with an anticancer drug, and it was shown that the released RPS3 binds to TLR4. Recombinant RPS3 induced maturation and activation of DCs, and following pulsing with tumor specific antigens, these DCs could be used as a vaccine to significantly increase tumor specific CD8+IFN-γ+ T cells, and provide both tumor prevention and tumor treatment effects. The effect of RPS3 on DC maturation and its utility as a vaccine were shown to be dependent on TLR4 using TLR4 knockout mice. Conclusions This study therefore proved that human cancer cell-derived RPS3, a novel TLR4 ligand, has great potential as an adjuvant in tumor-specific antigen DC-based vaccines.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article
– Name: Format
  Label: File Description
  Group: SrcInfo
  Data: electronic resource
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 2051-1426
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
  Data: http://link.springer.com/article/10.1186/s40425-019-0539-7; https://doaj.org/toc/2051-1426
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1186/s40425-019-0539-7
– Name: URL
  Label: Access URL
  Group: URL
  Data: <link linkTarget="URL" linkTerm="https://doaj.org/article/1cd143757e744b09a088290bbaa52a8e" linkWindow="_blank">https://doaj.org/article/1cd143757e744b09a088290bbaa52a8e</link>
– Name: AN
  Label: Accession Number
  Group: ID
  Data: edsdoj.1cd143757e744b09a088290bbaa52a8e
PLink https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.1cd143757e744b09a088290bbaa52a8e
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1186/s40425-019-0539-7
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 13
        StartPage: 1
    Subjects:
      – SubjectFull: Dendritic cell (DC)
        Type: general
      – SubjectFull: Toll-like receptor 4 (TLR4)
        Type: general
      – SubjectFull: DC based vaccine
        Type: general
      – SubjectFull: 40S ribosomal protein S3 (RPS3)
        Type: general
      – SubjectFull: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
        Type: general
      – SubjectFull: RC254-282
        Type: general
    Titles:
      – TitleFull: A novel TLR4 binding protein, 40S ribosomal protein S3, has potential utility as an adjuvant in a dendritic cell-based vaccine
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Hyun Jin Park
      – PersonEntity:
          Name:
            NameFull: Gun-Young Jang
      – PersonEntity:
          Name:
            NameFull: Young Seob Kim
      – PersonEntity:
          Name:
            NameFull: Jung Hwa Park
      – PersonEntity:
          Name:
            NameFull: Sung Eun Lee
      – PersonEntity:
          Name:
            NameFull: Manh-Cuong Vo
      – PersonEntity:
          Name:
            NameFull: Je-Jung Lee
      – PersonEntity:
          Name:
            NameFull: Hee Dong Han
      – PersonEntity:
          Name:
            NameFull: In Duk Jung
      – PersonEntity:
          Name:
            NameFull: Tae Heung Kang
      – PersonEntity:
          Name:
            NameFull: Yeong-Min Park
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 02
              Type: published
              Y: 2019
          Identifiers:
            – Type: issn-print
              Value: 20511426
          Numbering:
            – Type: volume
              Value: 7
            – Type: issue
              Value: 1
          Titles:
            – TitleFull: Journal for ImmunoTherapy of Cancer
              Type: main
ResultId 1