CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors

Walens, Andrea; DiMarco, Ashley V.; Lupo, Ryan; Kroger, Benjamin; Damrauer, Jeffrey S.; Alvarez, James V.

doi:10.7554/elife.43653

Cited by 151 publications

(102 citation statements)

References 50 publications

(63 reference statements)

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“…Residual Her2-driven breast tumors, responsible for cancer recurrence, are characterized by a pro-inflammatory gene expression program, including CCL5 [153]. High levels of CCL5 decreased the time between tumor treatment and recurrence [153]. CCL5 was found to promote tumor recurrence by recruiting CCR5-expressing macrophages, which contribute to collagen deposition in residual tumors.…”

Section: Breast Cancermentioning

confidence: 97%

“…In breast cancer, a population of residual tumor cells can survive after treatment and persist in a dormant state for many years. Residual Her2-driven breast tumors, responsible for cancer recurrence, are characterized by a pro-inflammatory gene expression program, including CCL5 [153]. High levels of CCL5 decreased the time between tumor treatment and recurrence [153].…”

Section: Breast Cancermentioning

confidence: 99%

See 1 more Smart Citation

The CCL5/CCR5 Axis in Cancer Progression

Aldinucci

Borghese

Casagrande

2020

Cancers

263

191

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Tumor cells can “hijack” chemokine networks to support tumor progression. In this context, the C-C chemokine ligand 5/C-C chemokine receptor type 5 (CCL5/CCR5) axis is gaining increasing attention, since abnormal expression and activity of CCL5 and its receptor CCR5 have been found in hematological malignancies and solid tumors. Numerous preclinical in vitro and in vivo studies have shown a key role of the CCL5/CCR5 axis in cancer, and thus provided the rationale for clinical trials using the repurposed drug maraviroc, a CCR5 antagonist used to treat HIV/AIDS. This review summarizes current knowledge on the role of the CCL5/CCR5 axis in cancer. First, it describes the involvement of the CCL5/CCR5 axis in cancer progression, including autocrine and paracrine tumor growth, ECM (extracellular matrix) remodeling and migration, cancer stem cell expansion, DNA damage repair, metabolic reprogramming, and angiogenesis. Then, it focuses on individual hematological and solid tumors in which CCL5 and CCR5 have been studied preclinically. Finally, it discusses clinical trials of strategies to counteract the CCL5/CCR5 axis in different cancers using maraviroc or therapeutic monoclonal antibodies.

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Section: Breast Cancermentioning

confidence: 97%

Section: Breast Cancermentioning

confidence: 99%

The CCL5/CCR5 Axis in Cancer Progression

Aldinucci

Borghese

Casagrande

2020

Cancers

263

191

View full text Add to dashboard Cite

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“…Along these lines, it was observed that more TNF-, CCL5 and IL-10 are produced by LCLs with higher levels of spontaneous lytic EBV reactivation 74 . These might inhibit the immune control by cytotoxic lymphocytes and recruit immunosuppressive myeloid cells 75 . Indeed, monocytes attracted by CCL5 into the Hodgkin's lymphoma microenvironment support tumor growth in a xenograft model through their immune suppressive activities 76 .…”

Section: Oncogenesis With Lytic Replicationmentioning

confidence: 99%

Latency and lytic replication in Epstein–Barr virus-associated oncogenesis

2019

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Epstein-Barr virus (EBV) was the first tumour virus identified in humans. The virus is primarily associated with lymphomas and epithelial cell cancers. These tumours express latent EBV antigens and the oncogenic potential of individual latent EBV proteins has been extensively explored. Nevertheless, it was presumed that the pro-proliferative and anti-apoptotic functions of these oncogenes allow the virus to persist in humans; however, recent evidence suggests that cellular transformation is not required for virus maintenance. Vice versa, lytic EBV replication was assumed to destroy latently infected cells and thereby inhibit tumorigenesis, but at least the initiation of the lytic cycle has now been shown to support EBV-driven malignancies. In addition to these changes in the roles of latent and lytic EBV proteins during tumorigenesis, the function of non-coding RNAs has become clearer, suggesting that they might mainly mediate immune escape rather than cellular transformation. In this Review, these recent findings will be discussed with respect to the role of EBV-encoded oncogenes in viral persistence and the contributions of lytic replication as well as non-coding RNAs in virus-driven tumour formation. Accordingly, early lytic EBV antigens and attenuated viruses without oncogenes and microRNAs could be harnessed for immunotherapies and vaccination. AbstractEpstein-Barr virus (EBV) was the first tumor virus identified in humans. It is primarily associated with lymphomas and epithelial cell cancers. These tumors express latent EBV antigens and the oncogenic potential of individual latent EBV proteins has been extensively explored.Nevertheless, it was presumed that the pro-proliferative and anti-apoptotic functions of these oncogenes allow the virus to persist in humans; however, recent evidence suggests that cellular transformation is not required for virus maintenance. Vice versa, lytic EBV replication was assumed to destroy latently infected cells and thereby inhibit tumorigenesis, but at least the initiation of the lytic cycle has now been shown to support EBV-driven malignancies. In addition to these changes in the roles of latent and lytic EBV proteins during tumourigenesis, the function of non-translated RNAs has become clearer, suggesting that they might mainly mediate immune escape rather than cellular transformation. In this Review, these recent findings will be discussed with respect to the role of EBV-encoded oncogenes in viral persistence and the contributions of lytic replication as well as non-translated RNAs in virus-driven tumor formation. Accordingly, early lytic EBV antigens and attenuated viruses without oncogenes and miRNAs could be harnessed for immunotherapies and vaccination. Table of contents blurb (40-50 words max.)Epstein-Barr virus (EBV) establishes latent and persistent infections in humans, and is associated with several cancers. In this Review, Münz discusses the evidence for EBV persistence without B cell transformation and the role of early abortive lytic replication, as well as non...

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“…Macrophage adhesion regulated by integrin induces lymphovascular dissemination in BC (55). CCL5 induced recurrence of BC via aggregation of macrophages in residual tumors (56). High expression of mast cells induced the tumor size and the incidence of spontaneous metastasis in BC mice (57).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Identified 17 Immune Genes as Prognostic Biomarkers for Breast Cancer: Application Study Based on Artificial Intelligence Algorithms

Zhang

et al. 2020

Front. Oncol.

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An increasing body of evidence supports the association of immune genes with tumorigenesis and prognosis of breast cancer (BC). This research aims at exploring potential regulatory mechanisms and identifying immunogenic prognostic markers for BC, which were used to construct a prognostic signature for disease-free survival (DFS) of BC based on artificial intelligence algorithms. Differentially expressed immune genes were identified between normal tissues and tumor tissues. Univariate Cox regression identified potential prognostic immune genes. Thirty-four transcription factors and 34 immune genes were used to develop an immune regulatory network. The artificial intelligence survival prediction system was developed based on three artificial intelligence algorithms. Multivariate Cox analyses determined 17 immune genes (ADAMTS8, IFNG,

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CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors

Cited by 151 publications

References 50 publications

The CCL5/CCR5 Axis in Cancer Progression

The CCL5/CCR5 Axis in Cancer Progression

Latency and lytic replication in Epstein–Barr virus-associated oncogenesis

Bioinformatics Identified 17 Immune Genes as Prognostic Biomarkers for Breast Cancer: Application Study Based on Artificial Intelligence Algorithms

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