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HLA-DR expression in cytotoxic T lymphocytes

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dc.contributor.authorSalvador, Rute
dc.contributor.authorCorreia, Bruna Filipa
dc.contributor.authorGrosa, Daniela
dc.contributor.authorMartins, Telma
dc.contributor.authorSoares Baal, Suelen Cristina
dc.contributor.authorSaraiva, Diana Pereira
dc.contributor.authorCristóvão-Ferreira, Sofia
dc.contributor.authorPereira, Isabel Lopes
dc.contributor.authorRebelo de Almeida, Cátia
dc.contributor.authorFior, Rita
dc.contributor.authorJacinto, Antonio
dc.contributor.authorMathias, Carolina
dc.contributor.authorBraga, Sofia
dc.contributor.authorCabral, M. Guadalupe
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.pblFrontiers
dc.date.accessioned2026-01-14T15:42:11Z
dc.date.available2026-01-14T15:42:11Z
dc.date.issued2025
dc.descriptionFunding Information: The author(s) declare financial support was received for the research and/or publication of this article. The funding was provided through the Terry Fox Research Grant 2019 from Liga Portuguesa Contra o Cancro, as well as grants from Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia (PD/BD/114023/2015 for DPS, SFRH/BD/148422/2019 for RS and 2021.08031.BD for BC), CAPES \u2013 Print (88887.936433/2024-00 for SS), CNPQ (444065/2023-7); iNOVA4Health (UIDB/04462/2020) and LS4FUTURE (LA/P/0087/2020). Funding Information: The author(s) declare financial support was received for the research and/or publication of this article. The funding was provided through the Terry Fox Research Grant 2019 from Liga Portuguesa Contra o Cancro, as well as grants from Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia (PD/BD/114023/2015 for DPS, SFRH/BD/148422/2019 for RS and 2021.08031.BD for BC), CAPES \u2013 Print (88887.936433/2024-00 for SS), CNPQ (444065/2023-7); iNOVA4Health (UIDB/04462/2020) and LS4FUTURE (LA/P/0087/2020). Acknowledgments Publisher Copyright: Copyright © 2025 Salvador, Correia, Grosa, Martins, Soares Baal, Saraiva, Cristóvão-Ferreira, Pereira, Rebelo de Almeida, Fior, Jacinto, Mathias, Braga and Cabral.
dc.description.abstractT cell-based therapies, involving ex vivo expansion of patients’ T lymphocytes, hold significant promise for chemotherapy resistant cases of breast cancer (BC), although their effectiveness remains challenging. Building on our previous findings that the expression of the antigen presenting molecule, HLA-DR, is crucial on tumor-infiltrating cytotoxic T lymphocytes (CTLs) for a favorable response to neoadjuvant chemotherapy, we further investigated the role of HLA-DR-expressing CTLs in anti-tumor responses and evaluated strategies to amplify these cells. Through in vitro and in vivo experiments, we demonstrated that HLA-DR expression on CTLs is important for effective tumor cell elimination. Notably, blocking HLA-DR or depleting CD4+ T cells impaired CTLs activation, suggesting a critical role for antigen presentation by CTLs to CD4+ T cells through HLA-DR in promoting robust anti-tumor responses. Based on these findings we optimized an ex vivo stimulation protocol that increases the proportion of HLA-DR+CTLs with improved cytotoxicity, prioritizing cell quality over yield. Moreover, we showed that adding anti-PD-1 to the stimulation, further upregulated HLA-DR expression, and intensified CTLs’ cytotoxic ability. This aligns with our in silico analysis suggesting a potential regulatory link between PD-1 and HLA-DR via non-coding RNAs. Overall, our findings open new avenues for advancing T cell-based therapies and improve the outcomes of chemotherapy-resistant-BC.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent6853956
dc.identifier.doi10.3389/fimmu.2025.1653970
dc.identifier.issn1664-3224
dc.identifier.otherPURE: 132126748
dc.identifier.otherPURE UUID: 5dfeddd2-15bc-4ec1-955b-cc689253ba3d
dc.identifier.otherScopus: 105017832822
dc.identifier.otherPubMed: 41050699
dc.identifier.otherORCID: /0000-0002-4193-6089/work/199854218
dc.identifier.urihttp://hdl.handle.net/10362/198946
dc.identifier.urlhttps://www.scopus.com/pages/publications/105017832822
dc.language.isoeng
dc.peerreviewedyes
dc.subject3D co-cultures
dc.subjectadoptive T cell therapy
dc.subjectbreast cancer
dc.subjectcytotoxic T lymphocytes
dc.subjectcytotoxicity
dc.subjectimmunomodulation
dc.subjectimmunotherapy
dc.subjectImmunology and Allergy
dc.subjectImmunology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleHLA-DR expression in cytotoxic T lymphocytesen
dc.title.subtitlea key to boost the therapeutic potential of T cell-based strategies for breast canceren
dc.typejournal article
degois.publication.titleFrontiers in Immunology
degois.publication.volume16
dspace.entity.typePublication
rcaap.rightsopenAccess

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