دورية أكاديمية
Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer.
| العنوان: | Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. |
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| المؤلفون: | Hermida-Prado, Francisco, Xie, Yingtian, Sherman, Shira, Nagy, Zsuzsanna, Russo, Douglas, Akhshi, Tara, Chu, Zhengtao, Feit, Avery, Campisi, Marco, Chen, Minyue, Nardone, Agostina, Guarducci, Cristina, Lim, Klothilda, Font-Tello, Alba, Lee, Irene, García-Pedrero, Juana, Cañadas, Israel, Agudo, Judith, Huang, Ying, Sella, Tal, Jin, Qingchun, Tayob, Nabihah, Mittendorf, Elizabeth A, Tolaney, Sara M, Qiu, Xintao, Long, Henry, Symmans, William F, Lin, Jia-Ren, Santagata, Sandro, Bedrosian, Isabelle, Yardley, Denise A, Mayer, Ingrid A, Richardson, Edward T, Oliveira, Giacomo, Wu, Catherine J, Schuster, Eugene F, Dowsett, Mitch, Welm, Alana L, Barbie, David, Metzger, Otto, Jeselsohn, Rinath |
| المصدر: | Cancer Res ; ISSN:1538-7445 ; Volume:83 ; Issue:19 |
| بيانات النشر: | Silverchair Information Systems |
| سنة النشر: | 2023 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1158/0008-5472.CAN-23-1711Test; https://pubmed.ncbi.nlm.nih.gov/37450351Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543960Test/ |
| DOI: | 10.1158/0008-5472.CAN-23-1711 |
| الإتاحة: | https://doi.org/10.1158/0008-5472.CAN-23-1711Test https://pubmed.ncbi.nlm.nih.gov/37450351Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543960Test/ |
| حقوق: | ©2023 The Authors; Published by the American Association for Cancer Research. |
| رقم الانضمام: | edsbas.517EE385 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/0008-5472.CAN-23-1711 |
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