dc.contributor.author | Hermida-Prado, F | |
dc.contributor.author | Xie, Y | |
dc.contributor.author | Sherman, S | |
dc.contributor.author | Nagy, Z | |
dc.contributor.author | Russo, D | |
dc.contributor.author | Akhshi, T | |
dc.contributor.author | Chu, Z | |
dc.contributor.author | Feit, A | |
dc.contributor.author | Campisi, M | |
dc.contributor.author | Chen, M | |
dc.contributor.author | Nardone, A | |
dc.contributor.author | Guarducci, C | |
dc.contributor.author | Lim, K | |
dc.contributor.author | Font-Tello, A | |
dc.contributor.author | Lee, I | |
dc.contributor.author | García-Pedrero, J | |
dc.contributor.author | Cañadas, I | |
dc.contributor.author | Agudo, J | |
dc.contributor.author | Huang, Y | |
dc.contributor.author | Sella, T | |
dc.contributor.author | Jin, Q | |
dc.contributor.author | Tayob, N | |
dc.contributor.author | Mittendorf, EA | |
dc.contributor.author | Tolaney, SM | |
dc.contributor.author | Qiu, X | |
dc.contributor.author | Long, H | |
dc.contributor.author | Symmans, WF | |
dc.contributor.author | Lin, J-R | |
dc.contributor.author | Santagata, S | |
dc.contributor.author | Bedrosian, I | |
dc.contributor.author | Yardley, DA | |
dc.contributor.author | Mayer, IA | |
dc.contributor.author | Richardson, ET | |
dc.contributor.author | Oliveira, G | |
dc.contributor.author | Wu, CJ | |
dc.contributor.author | Schuster, EF | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Welm, AL | |
dc.contributor.author | Barbie, D | |
dc.contributor.author | Metzger, O | |
dc.contributor.author | Jeselsohn, R | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-09-29T11:38:43Z | |
dc.date.available | 2023-09-29T11:38:43Z | |
dc.date.issued | 2023-10-02 | |
dc.identifier | 727814 | |
dc.identifier.citation | Cancer Research, 2023, pp. CAN-23-1711 - | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5995 | |
dc.identifier.eissn | 1538-7445 | |
dc.identifier.eissn | 1538-7445 | |
dc.identifier.doi | 10.1158/0008-5472.CAN-23-1711 | |
dc.description.abstract | UNLABELLED: Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor-positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated β2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of ET on cancer cells were explored, which revealed that ET plays a crucial role in facilitating the chromatin binding of RelA, a key component of the NF-κB complex. Consequently, heightened NF-κB signaling enhanced the response to interferon-gamma, leading to the upregulation of β2-microglobulin and other antigen presentation-related genes. Further, modulation of NF-κB signaling using a SMAC mimetic in conjunction with ET augmented T-cell migration and enhanced MHC-I-specific T-cell-mediated cytotoxicity. Remarkably, the combination of ET and SMAC mimetics, which also blocks prosurvival effects of NF-κB signaling through the degradation of inhibitors of apoptosis proteins, elicited tumor regression through cell autonomous mechanisms, providing additional support for their combined use in HR+ breast cancer. SIGNIFICANCE: Adding SMAC mimetics to endocrine therapy enhances tumor regression in a cell autonomous manner while increasing tumor immunogenicity, indicating that this combination could be an effective treatment for HR+ patients with breast cancer. | |
dc.format | Print-Electronic | |
dc.format.extent | CAN-23-1711 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Cancer Research | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-07-12 | |
dc.date.updated | 2023-09-29T11:38:16Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1158/0008-5472.CAN-23-1711 | |
rioxxterms.licenseref.startdate | 2023-07-14 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37450351 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine Therapy Resistance | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Closed research teams/Endocrinology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1158/0008-5472.can-23-1711 | |
icr.researchteam | Endocrine Therapy Resist | |
icr.researchteam | Endocrinology | |
dc.contributor.icrauthor | Schuster, Eugene | |
icr.provenance | Deposited by Mr Arek Surman on 2023-09-29. Deposit type is initial. No. of files: 1. Files: can-23-1711.pdf | |