Immune-based approaches to improve Breast Cancer management

Team Members: Rute Salvador, Bruna Correia, António Jacinto, Maria Guadalupe Cabral (IR: guadalupe.cabral@nms.unl.pt)

Objective:

Breast cancer (BC) is the most common malignancy in women worldwide. Despite the vast ongoing research efforts, it remains a challenging disease to treat. Increasing evidences have been highlighting the role of inflammation and immune players in cancer progression and response to conventional treatments. Therefore, it is believed that a deeper understanding of BC immunobiology is needed for the implementation of more efficient and tailored treatments for this disease. Using patients’ clinical samples, our research is focused on finding particular immune traces in the tumor microenvironment of BC,  that could be translated into accurate predictive/prognostic biomarkers or into new target therapies, ultimately aiming to ameliorate BC patients’ care.

Publications: 

• Saraiva DP, Correia BF, Salvador R, De Sousa N, Jacinto A, Braga S, Cabral MG. 2021. Circulating Low Density Neutrophils of Breast Cancer Patients are Associated with their Worse Prognosis due to the Impairment of T cell Responses. Oncotarget. 12(24):2388-2403. DOI: 10.18632/oncotarget.28135.
• Saraiva DP, Azeredo-Lopes S, Antunes A, Salvador R, Borralho P, Assis B, Pereira, IL, Seabra Z, Negreiros I, Jacinto A, Braga S, Cabral MG. 2021. Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer. Cancers 13(15):3841. DOI: 10.3390/cancers1315384.
• Saraiva DP, Matias AT, Braga S, Jacinto A, Cabral MG. 2020. Establishment of a 3D Coculture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies. Frontiers in Oncology 10:1543. Doi:10.3389/fonc.2020.01543.
• Saraiva DP, Jacinto A, Borralho P, Braga S, Cabral MG. 2018. HLA-DR expression in cytotoxic T Lymphocytes predicts Breast Cancer patients’ response to neoadjuvant chemotherapy. Frontiers in Immunology, 13:9:2605

Acknowledgments:

Liga Portuguesa Contra o Cancro (Terry Fox Research Grant 2019); Tagus Tank Consortium (Research Prize in Medicine 2018); Pfizer/Sociedade das Ciências Médicas (Clinical Research Prize 2019); iNOVA4Health (UID/Multi/04462/2013-Lisboa-01-0145FEDER-007)

• GutOnPhenols - Targeting the onset of gut inflammation with bioavailable polyphenol metabolites
  2020 - present
• ReInnervate - Mechanisms of reinnervation during skin repair: novel roles for intercellular communication
  2020 - present
• YAP-Meta - YAP metabolism interplay: a mechanism to stimulate retina regeneration
  2018 - present
• OntoGlia - How the brain’s immune cells develop: the role of Deleted in Autism-1 Related (DIA1R) in microglia ontogeny
  2018 - present
• Immune-based approaches to improve Breast Cancer management
  2017 - present
  (Funded by Liga Portuguesa Contra o Cancro (Bolsa de investigação Terry Fox 2019); Consórcio Tagus Tank (Prémio de investigação em medicina 2018); Pfizer/Sociedade das Ciências Médicas (Prémio em investigação clínica 2019); iNOVA4Health (UID/Multi/04462/2013-Lisboa-01-0145FEDER-007))
• MechanOJunctions - Occluding Junctions as novel regulators of epithelial mechanics during development and repair
  2018 to 2022
  (Funded by FCT — PTDC/BIA-BID/29709/2017)
• TarGut - Targeting early stages of gut inflammation
  2018 to 2022
  (Funded by FCT/PORLisboa — 02/SAICT/2017)
• RegenMeta - Interplay between metabolic reprogramming and cell fate plasticity: integrating metabolomics and transcriptomics to decipher the mechanisms of tissue regeneration.
  2017 - present

• Lourenço R, Brandão AS, Borbinha J, Gorgulho R, Jacinto A. Yap Regulates Müller Glia Reprogramming in Damaged Zebrafish Retinas. Front Cell Dev Biol. 2021 Sep 20;9:667796. https://dx.doi.org/10.3389/fcell.2021.667796
• Saraiva DP, Azeredo-Lopes S, Antunes A, Salvador R, Borralho P, Assis B, Pereira IL, Seabra Z, Negreiros I, Jacinto A, Braga S, Cabral MG. Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer. Cancers. 2021 Jul 30;13(15). https://dx.doi.org/10.3390/cancers13153841
• Paramos-de-Carvalho D, Martins I, Cristóvão AM, Dias AF, Neves-Silva D, Pereira T, Chapela D, Farinho A, Jacinto A, Saúde L. Targeting senescent cells improves functional recovery after spinal cord injury. Cell Rep. 2021 Jul 6;36(1):109334. https://dx.doi.org/10.1016/j.celrep.2021.109334
• Carvalho L, Patricio P, Ponte S, Heisenberg C-P, Almeida L, Nunes AS, Araújo NAM, Jacinto A. Occluding junctions as novel regulators of tissue mechanics during wound repair. J Cell Biol. 2018 Dec 3;217(12):4267–83. https://dx.doi.org/10.1083/jcb.201804048
• Brandão AS, Bensimon-Brito A, Lourenço R, Borbinha J, Soares AR, Mateus R, Jacinto A. Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration. J Cell Sci. 2019 Nov 14;132(22):jcs.231993. https://dx.doi.org/10.1242/jcs.231993
• Galliot B, Crescenzi M, Jacinto A, Tajbakhsh S. Trends in tissue repair and regeneration. Development. 2017 Feb 1;144(3):357–64. https://dx.doi.org/10.1242/dev.144279
• Ravasio A, Cheddadi I, Chen T, Pereira T, Ong HT, Bertocchi C, Brugues A, Jacinto A, Kabla AJ, Toyama Y, Trepat X, Gov N, Neves de Almeida L, Ladoux B. Gap geometry dictates epithelial closure efficiency. Nat Commun. 2015 Jul 9;6(1):7683. https://dx.doi.org/10.1038/ncomms8683
• Carvalho L, Jacinto A, Matova N. The Toll/NF-κB signaling pathway is required for epidermal wound repair in Drosophila. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5373–82. https://dx.doi.org/10.1073/pnas.1408224111
• Antunes M, Pereira T, Cordeiro JV, Almeida L, Jacinto A. Coordinated waves of actomyosin flow and apical cell constriction immediately after wounding. J Cell Biol. 2013 Jul 22;202(2):365–79. https://dx.doi.org/10.1083/jcb.201211039
• Cordeiro JV, Jacinto A. The role of transcription-independent damage signals in the initiation of epithelial wound healing. Nat Rev Mol Cell Biol. 2013 Apr;14(4):249–62. https://dx.doi.org/10.1038/nrm3541

• Pfizer Award for Basic Research, Antonio Jacinto (Team Member), 2021.
• Pfizer Award for Clinical Research, Guadalupe Cabral (Principal Investigator), 2019.
• Honour Medal (Silver) for Distinguished Service from the Ministry of Health, Portugal, Antonio Jacinto, 2014.
• Prize for Autoimmunity Clinical Research, Núcleo de Estudos de Doenças Autoimunes (NEDAI - SPMI), Antonio Jacinto, 2014.
• Apifarma prize for mobility, Antonio Jacinto, 2006.
• Pfizer Award for Basic Research, Antonio Jacinto (Principal Investigator), 2005.
• Prize for Best Poster Presentation, Santa Cruz Conference on Developmental Biology, USA, Antonio Jacinto, 2000.

• Maria Leonor Saúde, Institute of Molecular Medicine, University of Lisbon, Portugal
• Yi Feng, The University of Edinburgh, UK
• Carl-Philipp Heisenberg, Institute of Science and Technology, Austria