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West Ashley Library
9 a.m. – 7 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed
Phone: (843) 588-2001
Edgar Allan Poe/Sullivan's Island Library
Closed for renovations
Phone: (843) 883-3914
Wando Mount Pleasant Library
9 a.m. – 8 p.m.
Phone: (843) 805-6888
Village Library
9 a.m. – 6 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
9 a.m. – 8 p.m.
Phone: (843) 889-3300
Otranto Road Library
9 a.m. – 8 p.m.
Phone: (843) 572-4094
Mt. Pleasant Library
9 a.m. – 8 p.m.
Phone: (843) 849-6161
McClellanville Library
9 a.m. - 6 p.m.
Phone: (843) 887-3699
Keith Summey North Charleston Library
9 a.m. – 8 p.m.
Phone: (843) 744-2489
John's Island Library
9 a.m. – 8 p.m.
Phone: (843) 559-1945
Hurd/St. Andrews Library
9 a.m. – 8 p.m.
Phone: (843) 766-2546
Miss Jane's Building (Edisto Library Temporary Location)
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Phone: (843) 869-2355
Dorchester Road Library
9 a.m. – 8 p.m.
Phone: (843) 552-6466
John L. Dart Library
9 a.m. – 7 p.m.
Phone: (843) 722-7550
Baxter-Patrick James Island
9 a.m. – 8 p.m.
Phone: (843) 795-6679
Main Library
9 a.m. – 8 p.m.
Phone: (843) 805-6930
Bees Ferry West Ashley Library
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Phone: (843) 805-6892
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9 a.m. - 5 p.m.
Phone: (843) 805-6909
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Neoadjuvant immune checkpoint blockade triggers persistent and systemic Treg activation which blunts therapeutic efficacy against metastatic spread of breast tumors.
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- Author(s): Blomberg, Olga S.; Kos, Kevin; Spagnuolo, Lorenzo; Isaeva, Olga I.; Garner, Hannah; Wellenstein, Max D.; Bakker, Noor; Duits, Danique E.M.; Kersten, Kelly; Klarenbeek, Sjoerd; Hau, Cheei-Sing; Kaldenbach, Daphne; Raeven, Elisabeth A.M.; Vrijland, Kim; Kok, Marleen; de Visser, Karin E.
- Source:
OncoImmunology; 2023, Vol. 12 Issue 1, p1-16, 16p- Subject Terms:
- Source:
- Additional Information
- Abstract: The clinical successes of immune checkpoint blockade (ICB) in advanced cancer patients have recently spurred the clinical implementation of ICB in the neoadjuvant and perioperative setting. However, how neoadjuvant ICB therapy affects the systemic immune landscape and metastatic spread remains to be established. Tumors promote both local and systemic expansion of regulatory T cells (T
regs ), which are key orchestrators of tumor-induced immunosuppression, contributing to immune evasion, tumor progression and metastasis. Tregs express inhibitory immune checkpoint molecules and thus may be unintended targets for ICB therapy counteracting its efficacy. Using ICB-refractory models of spontaneous primary and metastatic breast cancer that recapitulate the poor ICB response of breast cancer patients, we observed that combined anti-PD-1 and anti-CTLA-4 therapy inadvertently promotes proliferation and activation of Tregs in the tumor, tumor-draining lymph node and circulation. Also in breast cancer patients, Treg levels were elevated upon ICB. Depletion of Tregs during neoadjuvant ICB in tumor-bearing mice not only reshaped the intratumoral immune landscape into a state favorable for ICB response but also induced profound and persistent alterations in systemic immunity, characterized by elevated CD8+ T cells and NK cells and durable T cell activation that was maintained after treatment cessation. While depletion of Tregs in combination with neoadjuvant ICB did not inhibit primary tumor growth, it prolonged metastasis-related survival driven predominantly by CD8+ T cells. This study demonstrates that neoadjuvant ICB therapy of breast cancer can be empowered by simultaneous targeting of Tregs, extending metastasis-related survival, independent of a primary tumor response. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of OncoImmunology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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