CCL2/CCR2 signaling in cancer pathogenesis

Hao, Qiongyu; Vadgama, Jaydutt V.; Wang, Piwen

doi:10.1186/s12964-020-00589-8

Cited by 201 publications

(160 citation statements)

References 176 publications

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“…However, recent studies have highlighted CCR2 as the primary driver of myelomonocytic recruitment during inflammation [ 35 ]. In addition, the importance of chemokines and their receptors in regulating anti-tumor immunity and tumor metastases were recently reviewed [ 36 , 37 , 38 ], including the dominant role of CCR2 in promoting recruitment of monocytes with pro-tumorigenic and pro-metastatic activities. Consistent with this, ongoing clinical trials have reported encouraging results of CCR2 inhibitors, especially as combination therapies, in patients with pancreatic cancers, hepatocellular carcinomas and ovarian cancers [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma

Mittal

Wang

Akimova

et al. 2020

Cancers

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Host anti-tumor immunity can be hindered by various mechanisms present within the tumor microenvironment, including the actions of myeloid-derived suppressor cells (MDSCs). We investigated the role of the CCR2/MCP-1 pathway in MDSC-associated tumor progression in murine lung cancer models. Phenotypic profiling revealed maximal expression of CCR2 by tumor-resident MDSCs, and MCP-1 by transplanted TC1 tumor cells, respectively. Use of CCR2-knockout (CCR2-KO) mice showed dependence of tumor growth on CCR2 signaling. Tumors in CCR2-KO mice had fewer CCR2low MDSCs, CD4 T cells and Tregs than WT mice, and increased infiltration by CD8 T cells producing IFN-γ and granzyme-B. Effects were MDSC specific, since WT and CCR2-KO conventional T (Tcon) cells had comparable proliferation and production of inflammatory cytokines, and suppressive functions of WT and CCR2-KO Foxp3+ Treg cells were also similar. We used a thioglycolate-induced peritonitis model to demonstrate a role for CCR2/MCP-1 in trafficking of CCR2+ cells to an inflammatory site, and showed the ability of a CCR2 antagonist to inhibit such trafficking. Use of this CCR2 antagonist promoted anti-tumor immunity and limited tumor growth. In summary, tumor cells are the prime source of MCP-1 that promotes MDSC recruitment, and our genetic and pharmacologic data demonstrate that CCR2 targeting may be an important component of cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma

Mittal

Wang

Akimova

et al. 2020

Cancers

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“…Chemokine C-C motif ligand 2 (CCL2), is a well-known cytokine belonging to the CC chemokine family 9, which can affect drug sensitivity in both paracrine and autocrine manners ( Hao et al, 2020 ). CCL2 expression has been related to tumor invasion, metastasis, and drug resistance ( Zhong et al, 2018 ; Dutta et al, 2020 ; Hao et al, 2020 ). Xu et al (2018b) have found that DPP-resistant gastric cancer cell lines, such as BGC823/DDP cells and SGC7901/DDP cells secrete more CCL2 to maintain DDP resistance.…”

Section: Dual Roles Of Autophagy In Chemoresistance Of Gastric Cancermentioning

confidence: 99%

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

Tang

et al. 2020

Front. Cell Dev. Biol.

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Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.

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“…TAMs are believed to originate in the bone marrow as monocytes which are then recruited to the primary tumor via the CCL2/CCR2 signaling axis [ 29 ]. However, studies have shown that even tissue-resident macrophages derived from the YS or FL can be reprogrammed in-situ by signals derived from tumors cells.…”

Section: Tumor-associated Macrophages In Breast Cancermentioning

confidence: 99%

TIME Is a Great Healer—Targeting Myeloid Cells in the Tumor Immune Microenvironment to Improve Triple-Negative Breast Cancer Outcomes

Singh

Zhang

Rosen

2020

Cells

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The word myeloid is derived from the Greek word muelós which means “marrow”. Therefore, myeloid cells are described as cells that arise in the bone marrow. They can be distinguished from lymphoid cells based on their different differentiation trajectories—Lymphoid cells (B and T cells) are usually born in the bone marrow, but they need to migrate to lymphoid organs to mature and differentiate usually in response to antigens produced due to infections and diseases like cancer. On the other hand, myeloid cells do not follow this differentiation trajectory. They arise from the bone marrow, and do not need an encounter with antigens to gain their functionality. Thus, while lymphoid cells are a part of the adaptive immune system, myeloid cells are a part of the innate immune system. Hematopoiesis gives rise to two progenitor cells—the common myeloid progenitor (CMP) and the common lymphoid progenitor (CLP). The CMP can give rise to megakaryocytes, erythrocytes, mast cells and myeloblasts. Myeloblasts in turn lead to the formation of basophils, neutrophils, eosinophils and monocytes that can further differentiate into macrophages. This review will focus on macrophages as well as the phenotypes they acquire with the tumor immune microenvironment (TIME) in triple-negative breast cancer (TNBC). It will address how cancer cells in the tumor microenvironment (TME) recruit macrophages and may switch to recruiting neutrophils upon depletion of these tumor-associated macrophages (TAMs). Finally, it will also shed light on past and current treatment options that specifically target these cells and how those affect patient outcomes in TNBC.

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CCL2/CCR2 signaling in cancer pathogenesis

Cited by 201 publications

References 176 publications

The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma

The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

TIME Is a Great Healer—Targeting Myeloid Cells in the Tumor Immune Microenvironment to Improve Triple-Negative Breast Cancer Outcomes

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