In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 4968-4968
Abstract:
Patients with metastatic breast cancer (MBC) have limited therapeutic options and novel treatments are critically needed. Prior studies demonstrated that the p38 kinase (p38) promotes MBC, while the mechanisms remained unknown. Here, we provide evidence for a novel mechanism by which p38 promotes metastasis. Using triple-negative breast cancer models, we showed that a selective inhibitor of p38 (p38i) significantly reduced tumor growth, angiogenesis, and lung metastasis. Importantly, p38i decreased the accumulation of myeloid populations, namely myeloid-derived suppressor cells (MDSCs) and CD163+ tumor-associated macrophages (TAMs). p38 controlled the expression of tumor-derived chemokines/cytokines that facilitated the recruitment of pro-tumor myeloid populations. Depletion of MDSCs was accompanied by reduced TAM infiltration and phenocopied the anti-metastatic effects of p38i. Reciprocally, p38i increased tumor infiltration by cytotoxic CD8+ T cells. Metadata showed that a reduced CD163+/CD8+ expression ratio correlates with metastasis-free survival in breast cancer, suggesting that targeting p38 may improve clinical outcomes. This study highlights a novel p38-driven mechanism as a therapeutic target in MBC. Citation Format: Justin Zonneville, Sean Colligan, Paul Wallace, Scott I. Abrams, Andrei V. Bakin. Blockade of p38 kinase impedes the mobilization of myeloid populations that promote breast cancer metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4968.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2020-4968
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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