Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway

Liu, Chao; Yao, Zhaoying; Wang, Jianbo; Zhang, Wen; Yang, Yan; Zhang, Yan; Qu, Xinliang; Zhu, Yubing; Zou, Jianjun; Peng, Sishi; Zhao, Yan; Zhao, Shuli; He, Bangshun; Mi, Qiong‐Yu; Liu, Xiuting; Zhang, Xu; Du, Qianming

doi:10.1038/s41418-019-0460-0

Cited by 147 publications

(123 citation statements)

References 44 publications

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“…Decreased CAF and tumor xenograft growth [124] Repolarized immunosuppressive TAMs towards an anti-tumoral M1-like state in organoids from patients with metastatic CRC. Generated objective clinical responses in CRC patients (MARACON-001 phase I trial) [44] Reduced MSC-induced tumor xenograft growth in vivo [125] Anti-CCL5 antibodies Decreased in vitro growth and migration of tumor cells, xenograft growth, liver metastases, sensitized to PDGFRβ therapy [126] Inhibited the effects of macrophage CCL5: PDL-1 stabilization and inhibition of tumor killing by T cells [127] RNAi-CCL5 silencing Decreased tumor growth in immunocompetent syngeneic mice and reduced Treg infiltration [4] CCL5 knockout Decreased tumor growth and metastasis facilitating CD8+ T cell accumulation in the tumor site in CRC xenografts. Decreased resistance to anti-PD-1 therapy [128] Esophageal carcinoma Maraviroc, siRNA-CCL5 silencing Blocked tumor cell migration and invasion in vitro.…”

Section: Maravirocmentioning

confidence: 99%

The CCL5/CCR5 Axis in Cancer Progression

Aldinucci

Borghese

Casagrande

2020

Cancers

255

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: Maravirocmentioning

confidence: 99%

The CCL5/CCR5 Axis in Cancer Progression

Aldinucci

Borghese

Casagrande

2020

Cancers

255

191

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“…Its expression is elevated in breast cancer [ 60 ], glioblastoma multiforme [ 61 ], and hepatocellular carcinoma [ 62 ]. In a tumor, CCL5 expression is found in cancer cells [ 63 , 64 ], cancer-associated fibroblasts (CAF) [ 65 ], mesenchymal stem cells (MSC) [ 66 ], MDSC [ 67 ], TAM [ 68 , 69 , 70 , 71 ], and TIL [ 72 ]. CCL5 expression also occurs in lymphatic endothelial cells, which is crucial for the formation of the metastatic niche [ 73 ].…”

Section: Ccr5 Ligandsmentioning

confidence: 99%

“…In addition, CCL5 increases apoptosis resistance and drug resistance through the activation of Akt/PKB→NF-κB and STAT3 pathways [ 72 , 85 , 86 , 87 ]. It also causes an increase in programmed death-ligand 1 (PD-L1) expression on cancer cells, which protects them against cytotoxic lymphocytes [ 71 ].…”

Section: Ccr5 Ligandsmentioning

confidence: 99%

“…However, little is known about the interactions between cells in a tumor, particularly the direct or indirect influence of cancer cells on non-cancer cells and the interactions between non-cancer cells. Especially interesting are cancer-cell-induced changes in the expression of chemokines produced by cancer-associated cells, e.g., by TAM [ 68 , 69 , 70 , 71 , 257 , 258 ], MDSC [ 67 ], and CAF [ 65 ]. In a tumor, cancer cells are not isolated but interact with cancer-associated cells, and that is why these cells (e.g., TAM, TIL, MDSC, CAF) should be investigated more often to discover new mechanisms in a tumor.…”

Section: Further Direction In the Research On The Role Of CC Chemomentioning

confidence: 99%

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CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands

Korbecki

Grochans

Gutowska

et al. 2020

IJMS

218

176

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CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4+ and CD8+ lymphocytes, dendritic cells, eosinophils, macrophages, monocytes, and NK cells, as well in neoplasia. In this review, we discuss human CC motif chemokine ligands: CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 (CC motif chemokine receptor CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands). We present their functioning in human physiology and in neoplasia, including their role in the proliferation, apoptosis resistance, drug resistance, migration, and invasion of cancer cells. We discuss the significance of chemokine receptors in organ-specific metastasis, as well as the influence of each chemokine on the recruitment of various cells to the tumor niche, such as cancer-associated fibroblasts (CAF), Kupffer cells, myeloid-derived suppressor cells (MDSC), osteoclasts, tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and regulatory T cells (Treg). Finally, we show how the effect of the chemokines on vascular endothelial cells and lymphatic endothelial cells leads to angiogenesis and lymphangiogenesis.

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“…In macrophages, results vary depending on the research model: chronic hypoxia may decrease [157,205], have no influence [158,177], or increase [201] CCL5/RANTES expression. Nevertheless, in cancer, CCL5/RANTES expression does occur, among others, in TAM [102,[206][207][208], and for this reason, the mechanism of the effect of hypoxia on the expression of CCL5/RANTES in these cells requires further research.…”

Section: Effect Of Hypoxia On the Expression Of Ccl5/rantesmentioning

confidence: 99%

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Korbecki

Kojder

Barczak

et al. 2020

IJMS

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Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and tumor-associated macrophages (TAM) to a tumor niche.

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Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway

Cited by 147 publications

References 44 publications

The CCL5/CCR5 Axis in Cancer Progression

The CCL5/CCR5 Axis in Cancer Progression

CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

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