Publication
The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
| Summary: | It is well established that therapeutic impairment of Foxp3+ Treg in mice and humans favors immune rejection of solid tumors. Less explored is the impact Foxp3 allelic variants may have on tumor incidence, progression and therapy. In this work, we tested and demonstrate that the Foxp3fgfp reporter allele, found previously to either enhance or reduce Treg function in specific autoimmunity settings, confers increased anti-tumor immunity. Our conclusions stem out of the analysis of three tumor models of different tissue origin, in two murine genetic backgrounds. When compared to wild type animals, mice carrying the Foxp3fgfp allele spontaneously delay, reduce or prevent primary tumor growth, decrease metastasis growth, and potentiate the response to anti-CTLA4 monotherapy. These findings suggest allelic variances at the Foxp3 locus may serve as predictive indicators for personalized therapy and prognostics, and point at possible new therapeutic targets. |
|---|---|
| Main Authors: | Almeida-Santos, Jose |
| Other Authors: | Bergman, Marie-Louise; Jocelyne, Demengeot; Correia, Vasco; Caramalho, Iris; Cabral, Ines |
| Subject: | Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| Year: | 2019 |
| Country: | Portugal |
| Document type: | article |
| Access type: | open access |
| Associated institution: | Repositório do GIMM – Gulbenkian Institute for Molecular Medicine |
| Language: | English |
| Origin: | ARCA |
| _version_ | 1877783025053335552 |
|---|---|
| author | Almeida-Santos, Jose |
| author2 | Bergman, Marie-Louise Jocelyne, Demengeot Correia, Vasco Caramalho, Iris Cabral, Ines |
| author2_role | author author author author author |
| author_facet | Almeida-Santos, Jose Bergman, Marie-Louise Jocelyne, Demengeot Correia, Vasco Caramalho, Iris Cabral, Ines |
| author_role | author |
| contributor_name_str_mv | ARCA |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Almeida-Santos, Jose\",\"Person.identifier.orcid\":\"0000-0002-6212-3722\"},{\"Person.name\":\"Bergman, Marie-Louise\",\"Person.identifier.cienciaID\":\"D71C-9ED2-3824\",\"Person.identifier.orcid\":\"0000-0003-0691-4308\"},{\"Person.name\":\"Jocelyne, Demengeot\",\"Person.identifier.cienciaID\":\"3A12-B260-A36C\",\"Person.identifier.orcid\":\"0000-0002-4761-614X\",\"Person.identifier.researcherID\":\"K-8072-2014\",\"Person.identifier.scopusAuthorID\":\"6603702602\"},{\"Person.name\":\"Correia, Vasco\",\"Person.identifier.cienciaID\":\"151E-1B5E-DAE5\"},{\"Person.name\":\"Caramalho, Iris\",\"Person.identifier.orcid\":\"0000-0003-2479-7846\",\"Person.identifier.researcherID\":\"L-2491-2014\",\"Person.identifier.scopusAuthorID\":\"6507416937\"},{\"Person.name\":\"Cabral, Ines\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | ARCA |
| datacite.creators.creator.creatorName.fl_str_mv | Almeida-Santos, Jose Bergman, Marie-Louise Jocelyne, Demengeot Correia, Vasco Caramalho, Iris Cabral, Ines |
| datacite.date.Accepted.fl_str_mv | 2019-11-15T00:00:00Z |
| datacite.date.available.fl_str_mv | 2020-11-01T01:30:08Z |
| datacite.date.embargoed.fl_str_mv | 2020-11-01T01:30:08Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| datacite.titles.title.fl_str_mv | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| dc.contributor.none.fl_str_mv | ARCA |
| dc.creator.none.fl_str_mv | Almeida-Santos, Jose Bergman, Marie-Louise Jocelyne, Demengeot Correia, Vasco Caramalho, Iris Cabral, Ines |
| dc.date.Accepted.fl_str_mv | 2019-11-15T00:00:00Z |
| dc.date.available.fl_str_mv | 2020-11-01T01:30:08Z |
| dc.date.embargoed.fl_str_mv | 2020-11-01T01:30:08Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.7/926 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| dc.title.fl_str_mv | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | It is well established that therapeutic impairment of Foxp3+ Treg in mice and humans favors immune rejection of solid tumors. Less explored is the impact Foxp3 allelic variants may have on tumor incidence, progression and therapy. In this work, we tested and demonstrate that the Foxp3fgfp reporter allele, found previously to either enhance or reduce Treg function in specific autoimmunity settings, confers increased anti-tumor immunity. Our conclusions stem out of the analysis of three tumor models of different tissue origin, in two murine genetic backgrounds. When compared to wild type animals, mice carrying the Foxp3fgfp allele spontaneously delay, reduce or prevent primary tumor growth, decrease metastasis growth, and potentiate the response to anti-CTLA4 monotherapy. These findings suggest allelic variances at the Foxp3 locus may serve as predictive indicators for personalized therapy and prognostics, and point at possible new therapeutic targets. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://arca.gimm.pt/bitstreams/76df8bc9-91bb-4742-9a1d-e7a922a0e6ec/download |
| funder_facet_str_mv | FCT{{{_:::_}}}Fundação para a Ciência e a Tecnologia |
| funding.funder.alternateName_str_mv | FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia |
| funding.identifier_str_mv | SFRH/BPD/111454/2015 |
| funding.name_str_mv | OE |
| funding_str_mv | SFRH/BPD/111454/2015 info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F111454%2F2015/PT |
| id | arca_b4c5f0cda0369a7b83b0d50ca52be016 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.7/926 |
| inst_facet_str | urn:organizationAcronym:arca{{{_:::_}}}Repositório do GIMM – Gulbenkian Institute for Molecular Medicine |
| instacron_str | arca |
| institution | Repositório do GIMM – Gulbenkian Institute for Molecular Medicine |
| instname_str | Repositório do GIMM – Gulbenkian Institute for Molecular Medicine |
| language | eng |
| network_acronym_str | arca |
| network_name_str | ARCA |
| oai_identifier_str | oai:arca.gimm.pt:10400.7/926 |
| organization_str_mv | urn:organizationAcronym:arca |
| person_str_mv | Almeida-Santos, Jose Almeida-Santos, Jose http://orcid.org/0000-0002-6212-3722 0000-0002-6212-3722 Bergman, Marie-Louise Bergman, Marie-Louise https://www.ciencia-id.pt/D71C-9ED2-3824 D71C-9ED2-3824 http://orcid.org/0000-0003-0691-4308 0000-0003-0691-4308 Jocelyne, Demengeot Jocelyne, Demengeot https://www.ciencia-id.pt/3A12-B260-A36C 3A12-B260-A36C http://orcid.org/0000-0002-4761-614X 0000-0002-4761-614X Correia, Vasco Correia, Vasco https://www.ciencia-id.pt/151E-1B5E-DAE5 151E-1B5E-DAE5 Caramalho, Iris Caramalho, Iris http://orcid.org/0000-0003-2479-7846 0000-0003-2479-7846 Cabral, Ines |
| publishDate | 2019 |
| publisher.none.fl_str_mv | WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim |
| repo_facet_str | urn:repositoryAcronym:arca{{{_:::_}}}ARCA |
| reponame_str | ARCA |
| repository_id_str | urn:repositoryAcronym:arca |
| service_str_mv | urn:repositoryAcronym:arca |
| spelling | engWILEY‐VCH Verlag GmbH & Co. KGaA, Weinheimpt_PTIt is well established that therapeutic impairment of Foxp3+ Treg in mice and humans favors immune rejection of solid tumors. Less explored is the impact Foxp3 allelic variants may have on tumor incidence, progression and therapy. In this work, we tested and demonstrate that the Foxp3fgfp reporter allele, found previously to either enhance or reduce Treg function in specific autoimmunity settings, confers increased anti-tumor immunity. Our conclusions stem out of the analysis of three tumor models of different tissue origin, in two murine genetic backgrounds. When compared to wild type animals, mice carrying the Foxp3fgfp allele spontaneously delay, reduce or prevent primary tumor growth, decrease metastasis growth, and potentiate the response to anti-CTLA4 monotherapy. These findings suggest allelic variances at the Foxp3 locus may serve as predictive indicators for personalized therapy and prognostics, and point at possible new therapeutic targets.application/pdfpt_PTThe multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in micePersonalAlmeida-Santos, JoseDSpacehttp://dspace.org/items/9be95962-fe5c-44bc-893a-dfc9fdae528eDSpacehttp://dspace.org/items/9be95962-fe5c-44bc-893a-dfc9fdae528eAlmeida-SantosJoseORCIDhttp://orcid.org0000-0002-6212-3722PersonalBergman, Marie-LouiseDSpacehttp://dspace.org/items/07b1aa1a-30fd-4c6e-83d7-e2595887dd99DSpacehttp://dspace.org/items/07b1aa1a-30fd-4c6e-83d7-e2595887dd99BergmanMarie-LouiseCiência IDhttps://www.ciencia-id.ptD71C-9ED2-3824ORCIDhttp://orcid.org0000-0003-0691-4308PersonalJocelyne, DemengeotDSpacehttp://dspace.org/items/eda6ec95-9595-42b6-9dfe-078e88d8cb2bDSpacehttp://dspace.org/items/eda6ec95-9595-42b6-9dfe-078e88d8cb2bDemengeotJocelyneCiência IDhttps://www.ciencia-id.pt3A12-B260-A36CORCIDhttp://orcid.org0000-0002-4761-614XResearcher IDhttps://www.researcherid.comK-8072-2014Scopus Author IDhttps://www.scopus.com6603702602PersonalCorreia, VascoDSpacehttp://dspace.org/items/c80d7338-bec4-4bbb-8cbb-a370ed106aceDSpacehttp://dspace.org/items/c80d7338-bec4-4bbb-8cbb-a370ed106aceVieira CorreiaVascoCiência IDhttps://www.ciencia-id.pt151E-1B5E-DAE5PersonalCaramalho, IrisDSpacehttp://dspace.org/items/0dceaa72-3f12-4c2b-93ef-5bd1d224b2c9DSpacehttp://dspace.org/items/0dceaa72-3f12-4c2b-93ef-5bd1d224b2c9CaramalhoIrisORCIDhttp://orcid.org0000-0003-2479-7846Researcher IDhttps://www.researcherid.comL-2491-2014Scopus Author IDhttps://www.scopus.com6507416937Cabral, InesHostingInstitutionOrganizationalARCAe-mailmailto:arca.repository@gimm.ptarca.repository@gimm.ptDOIIsPartOf10.1002/eji.2019482512020-11-01T01:30:08Z2019-11-152019-11-15T00:00:00ZHandlehttp://hdl.handle.net/10400.7/926http://purl.org/coar/access_right/c_abf2open accessResearch Subject Categories::MEDICINEResearch Subject Categories::NATURAL SCIENCESTregFoxp3:GFP Allelic hypomorph variantTumor Immunology2457718 bytesFundação para a Ciência e a TecnologiaMolecular basis of the contribution of a common AIRE allelic variant to the targeting of organ-specific autoimmunity and quality of anti-tumor responsesinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F111454%2F2015/PTSFRH/BPD/111454/2015OECrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://arca.gimm.pt/bitstreams/76df8bc9-91bb-4742-9a1d-e7a922a0e6ec/downloadEuropean Journal of Immunology503439444 |
| spellingShingle | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice Almeida-Santos, Jose Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| status | SINGLETON |
| subject.fl_str_mv | Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| title | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| title_full | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| title_fullStr | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| title_full_unstemmed | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| title_short | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| title_sort | The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice |
| topic | Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| topic_facet | Research Subject Categories::MEDICINE Research Subject Categories::NATURAL SCIENCES Treg Foxp3:GFP Allelic hypomorph variant Tumor Immunology |
| url | http://hdl.handle.net/10400.7/926 |
| visible | 1 |