Academic Journal
View in EDS

Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models.

Bibliographic Details
Title: Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models.
Authors: Pieper, Alexander A., Zangl, Luke M., Speigelman, Dan V., Feils, Arika S., Hoefges, Anna, Jagodinsky, Justin C., Felder, Mildred A., Tsarovsky, Noah W., Arthur, Ian S., Brown, Ryan J., Birstler, Jen, Le, Trang, Carlson, Peter M., Bates, Amber M., Hank, Jacquelyn A., Rakhmilevich, Alexander L., Erbe, Amy K., Sondel, Paul M., Patel, Ravi B., Morris, Zachary S.
Source: Frontiers in Immunology; 11/15/2021, Vol. 12, p1-14, 14p
Subject Terms: MELANOMA, REGULATORY T cells, TUMOR-infiltrating immune cells, CPG nucleotides, BREAST cancer, VACCINE effectiveness
Abstract: Introduction: Combining CpG oligodeoxynucleotides with anti-OX40 agonist antibody (CpG+OX40) is able to generate an effective in situ vaccine in some tumor models, including the A20 lymphoma model. Immunologically "cold" tumors, which are typically less responsive to immunotherapy, are characterized by few tumor infiltrating lymphocytes (TILs), low mutation burden, and limited neoantigen expression. Radiation therapy (RT) can change the tumor microenvironment (TME) of an immunologically "cold" tumor. This study investigated the effect of combining RT with the in situ vaccine CpG+OX40 in immunologically "cold" tumor models. Methods: Mice bearing flank tumors (A20 lymphoma, B78 melanoma or 4T1 breast cancer) were treated with combinations of local RT, CpG, and/or OX40, and response to treatment was monitored. Flow cytometry and quantitative polymerase chain reaction (qPCR) experiments were conducted to study differences in the TME, secondary lymphoid organs, and immune activation after treatment. Results: An in situ vaccine regimen of CpG+OX40, which was effective in the A20 model, did not significantly improve tumor response or survival in the "cold" B78 and 4T1 models, as tested here. In both models, treatment with RT prior to CpG+OX40 enabled a local response to this in situ vaccine, significantly improving the anti-tumor response and survival compared to RT alone or CpG+OX40 alone. RT increased OX40 expression on tumor infiltrating CD4+ non-regulatory T cells. RT+CpG+OX40 increased the ratio of tumor-infiltrating effector T cells to T regulatory cells and significantly increased CD4+ and CD8+ T cell activation in the tumor draining lymph node (TDLN) and spleen. Conclusion: RT significantly improves the local anti-tumor effect of the in situ vaccine CpG+OX40 in immunologically "cold", solid, murine tumor models where RT or CpG+OX40 alone fail to stimulate tumor regression. [ABSTRACT FROM AUTHOR]
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edb&genre=article&issn=16643224&ISBN=&volume=12&issue=&date=20211115&spage=1&pages=1-14&title=Frontiers in Immunology&atitle=Radiation%20Augments%20the%20Local%20Anti-Tumor%20Effect%20of%20In%20Situ%20Vaccine%20With%20CpG-Oligodeoxynucleotides%20and%20Anti-OX40%20in%20Immunologically%20Cold%20Tumor%20Models.&aulast=Pieper%2C%20Alexander%20A.&id=DOI:10.3389/fimmu.2021.763888
    Name: Full Text Finder (for New FTF UI) (s8985755)
    Category: fullText
    Text: Find It @ SCU Libraries
    MouseOverText: Find It @ SCU Libraries
Header DbId: edb
DbLabel: Complementary Index
An: 153624575
RelevancyScore: 931
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 931.403259277344
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Pieper%2C+Alexander+A%2E%22">Pieper, Alexander A.</searchLink><br /><searchLink fieldCode="AR" term="%22Zangl%2C+Luke+M%2E%22">Zangl, Luke M.</searchLink><br /><searchLink fieldCode="AR" term="%22Speigelman%2C+Dan+V%2E%22">Speigelman, Dan V.</searchLink><br /><searchLink fieldCode="AR" term="%22Feils%2C+Arika+S%2E%22">Feils, Arika S.</searchLink><br /><searchLink fieldCode="AR" term="%22Hoefges%2C+Anna%22">Hoefges, Anna</searchLink><br /><searchLink fieldCode="AR" term="%22Jagodinsky%2C+Justin+C%2E%22">Jagodinsky, Justin C.</searchLink><br /><searchLink fieldCode="AR" term="%22Felder%2C+Mildred+A%2E%22">Felder, Mildred A.</searchLink><br /><searchLink fieldCode="AR" term="%22Tsarovsky%2C+Noah+W%2E%22">Tsarovsky, Noah W.</searchLink><br /><searchLink fieldCode="AR" term="%22Arthur%2C+Ian+S%2E%22">Arthur, Ian S.</searchLink><br /><searchLink fieldCode="AR" term="%22Brown%2C+Ryan+J%2E%22">Brown, Ryan J.</searchLink><br /><searchLink fieldCode="AR" term="%22Birstler%2C+Jen%22">Birstler, Jen</searchLink><br /><searchLink fieldCode="AR" term="%22Le%2C+Trang%22">Le, Trang</searchLink><br /><searchLink fieldCode="AR" term="%22Carlson%2C+Peter+M%2E%22">Carlson, Peter M.</searchLink><br /><searchLink fieldCode="AR" term="%22Bates%2C+Amber+M%2E%22">Bates, Amber M.</searchLink><br /><searchLink fieldCode="AR" term="%22Hank%2C+Jacquelyn+A%2E%22">Hank, Jacquelyn A.</searchLink><br /><searchLink fieldCode="AR" term="%22Rakhmilevich%2C+Alexander+L%2E%22">Rakhmilevich, Alexander L.</searchLink><br /><searchLink fieldCode="AR" term="%22Erbe%2C+Amy+K%2E%22">Erbe, Amy K.</searchLink><br /><searchLink fieldCode="AR" term="%22Sondel%2C+Paul+M%2E%22">Sondel, Paul M.</searchLink><br /><searchLink fieldCode="AR" term="%22Patel%2C+Ravi+B%2E%22">Patel, Ravi B.</searchLink><br /><searchLink fieldCode="AR" term="%22Morris%2C+Zachary+S%2E%22">Morris, Zachary S.</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Frontiers in Immunology; 11/15/2021, Vol. 12, p1-14, 14p
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22MELANOMA%22">MELANOMA</searchLink><br /><searchLink fieldCode="DE" term="%22REGULATORY+T+cells%22">REGULATORY T cells</searchLink><br /><searchLink fieldCode="DE" term="%22TUMOR-infiltrating+immune+cells%22">TUMOR-infiltrating immune cells</searchLink><br /><searchLink fieldCode="DE" term="%22CPG+nucleotides%22">CPG nucleotides</searchLink><br /><searchLink fieldCode="DE" term="%22BREAST+cancer%22">BREAST cancer</searchLink><br /><searchLink fieldCode="DE" term="%22VACCINE+effectiveness%22">VACCINE effectiveness</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Introduction: Combining CpG oligodeoxynucleotides with anti-OX40 agonist antibody (CpG+OX40) is able to generate an effective in situ vaccine in some tumor models, including the A20 lymphoma model. Immunologically "cold" tumors, which are typically less responsive to immunotherapy, are characterized by few tumor infiltrating lymphocytes (TILs), low mutation burden, and limited neoantigen expression. Radiation therapy (RT) can change the tumor microenvironment (TME) of an immunologically "cold" tumor. This study investigated the effect of combining RT with the in situ vaccine CpG+OX40 in immunologically "cold" tumor models. Methods: Mice bearing flank tumors (A20 lymphoma, B78 melanoma or 4T1 breast cancer) were treated with combinations of local RT, CpG, and/or OX40, and response to treatment was monitored. Flow cytometry and quantitative polymerase chain reaction (qPCR) experiments were conducted to study differences in the TME, secondary lymphoid organs, and immune activation after treatment. Results: An in situ vaccine regimen of CpG+OX40, which was effective in the A20 model, did not significantly improve tumor response or survival in the "cold" B78 and 4T1 models, as tested here. In both models, treatment with RT prior to CpG+OX40 enabled a local response to this in situ vaccine, significantly improving the anti-tumor response and survival compared to RT alone or CpG+OX40 alone. RT increased OX40 expression on tumor infiltrating CD4+ non-regulatory T cells. RT+CpG+OX40 increased the ratio of tumor-infiltrating effector T cells to T regulatory cells and significantly increased CD4+ and CD8+ T cell activation in the tumor draining lymph node (TDLN) and spleen. Conclusion: RT significantly improves the local anti-tumor effect of the in situ vaccine CpG+OX40 in immunologically "cold", solid, murine tumor models where RT or CpG+OX40 alone fail to stimulate tumor regression. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edb&AN=153624575
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.3389/fimmu.2021.763888
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 14
        StartPage: 1
    Subjects:
      – SubjectFull: MELANOMA
        Type: general
      – SubjectFull: REGULATORY T cells
        Type: general
      – SubjectFull: TUMOR-infiltrating immune cells
        Type: general
      – SubjectFull: CPG nucleotides
        Type: general
      – SubjectFull: BREAST cancer
        Type: general
      – SubjectFull: VACCINE effectiveness
        Type: general
    Titles:
      – TitleFull: Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Pieper, Alexander A.
      – PersonEntity:
          Name:
            NameFull: Zangl, Luke M.
      – PersonEntity:
          Name:
            NameFull: Speigelman, Dan V.
      – PersonEntity:
          Name:
            NameFull: Feils, Arika S.
      – PersonEntity:
          Name:
            NameFull: Hoefges, Anna
      – PersonEntity:
          Name:
            NameFull: Jagodinsky, Justin C.
      – PersonEntity:
          Name:
            NameFull: Felder, Mildred A.
      – PersonEntity:
          Name:
            NameFull: Tsarovsky, Noah W.
      – PersonEntity:
          Name:
            NameFull: Arthur, Ian S.
      – PersonEntity:
          Name:
            NameFull: Brown, Ryan J.
      – PersonEntity:
          Name:
            NameFull: Birstler, Jen
      – PersonEntity:
          Name:
            NameFull: Le, Trang
      – PersonEntity:
          Name:
            NameFull: Carlson, Peter M.
      – PersonEntity:
          Name:
            NameFull: Bates, Amber M.
      – PersonEntity:
          Name:
            NameFull: Hank, Jacquelyn A.
      – PersonEntity:
          Name:
            NameFull: Rakhmilevich, Alexander L.
      – PersonEntity:
          Name:
            NameFull: Erbe, Amy K.
      – PersonEntity:
          Name:
            NameFull: Sondel, Paul M.
      – PersonEntity:
          Name:
            NameFull: Patel, Ravi B.
      – PersonEntity:
          Name:
            NameFull: Morris, Zachary S.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 15
              M: 11
              Text: 11/15/2021
              Type: published
              Y: 2021
          Identifiers:
            – Type: issn-print
              Value: 16643224
          Numbering:
            – Type: volume
              Value: 12
          Titles:
            – TitleFull: Frontiers in Immunology
              Type: main
ResultId 1