Regulation of efferocytosis as a novel cancer therapy

Zhou, Yunxiang; Yao, Yanlai; Deng, Yongchuan; Shao, Anwen

doi:10.1186/s12964-020-00542-9

Cited by 47 publications

(30 citation statements)

References 143 publications

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“…Following apoptotic cell recognition and tethering, cytoskeletal rearrangement within macrophages occurs, leading to cell motility and phagosome formation to eventually engulf the apoptotic cell. Although it has been shown the ELMO/Dock180/Rac1 pathway is involved to complete the engulfment process, [ 14b,65 ] the precise molecular signaling pathways responsible for the initiation of cytoskeletal rearrangement and phagosome formation remain to be determined.…”

Section: Regulation Of Macrophage Phagocytosis Against Tumor Cellsmentioning

confidence: 99%

“…[ 79 ] Other investigation suggests that anti‐CD47 antibody can decrease the activity of Treg cells, thereby enhancing the activation of CD8+ T cells to achieve efficient antitumor potential. [ 65 ] These results indicate that the adaptive immune system, especially CD8+ cytotoxic T cell response, is also involved to generate antitumor efficacy in anti‐CD47 therapy. Considering that the expression of adaptive immune checkpoints in the tumor microenvironment attenuates the antitumor capability of T cells, the combination of adaptive checkpoint blockade with interference of CD47‐SIRPα signaling can be a promising therapeutic strategy to elicit synergistic anticancer effect.…”

Section: Therapeutic Strategies Targeting Macrophage Phagocytosismentioning

confidence: 99%

“…Currently, five types of Axl inhibitors have been reported, including small molecule inhibitors, monoclonal antibodies, soluble receptors, nucleotide aptamers, and natural compounds. [ 65,97 ] A small molecule inhibitor R428, also known as BGB324, has been widely used in preclinical investigations and is currently in clinical trials. [ 96,98 ] The therapeutic efficacy of nucleotide aptamers and antibodies are also under evaluation in preclinical studies.…”

Section: Therapeutic Strategies Targeting Macrophage Phagocytosismentioning

confidence: 99%

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Macrophage‐Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention

Zhou

Liu

Huang

2020

Adv Funct Materials

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Macrophages are one of the most abundant non‐malignant cells in the tumor microenvironment, playing critical roles in mediating tumor immunity. As important innate immune cells, macrophages possess the potential to engulf tumor cells and present tumor‐specific antigens for adaptive antitumor immunity induction, leading to growing interest in targeting macrophage phagocytosis for cancer immunotherapy. Nevertheless, live tumor cells have evolved to evade phagocytosis by macrophages via the extensive expression of anti‐phagocytic molecules, such as CD47. In addition, macrophages also rapidly recognize and engulf apoptotic cells (efferocytosis) in the tumor microenvironment, which inhibits inflammatory responses and facilitates immune escape of tumor cells. Thus, intervention of macrophage phagocytosis by blocking anti‐phagocytic signals on live tumor cells or inhibiting tumor efferocytosis presents a promising strategy for the development of cancer immunotherapies. Here, the regulation of macrophage‐mediated tumor cell phagocytosis is first summarized, followed by an overview of strategies targeting macrophage phagocytosis for the development of antitumor therapies. Given the potential off‐target effects associated with the administration of traditional therapeutics (for example, monoclonal antibodies and small molecule inhibitors), the opportunity for nanomedicine in macrophage phagocytosis intervention is highlighted.

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Section: Regulation Of Macrophage Phagocytosis Against Tumor Cellsmentioning

confidence: 99%

Section: Therapeutic Strategies Targeting Macrophage Phagocytosismentioning

confidence: 99%

Section: Therapeutic Strategies Targeting Macrophage Phagocytosismentioning

confidence: 99%

See 1 more Smart Citation

Macrophage‐Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention

Zhou

Liu

Huang

2020

Adv Funct Materials

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“…Agents that promote macrophage efflux or enhance efferocytosis showed promising effects on the reduction of ACS events by restricting the expression of netrin-1 and delivering nanoparticles loaded with siRNA to M1 macrophages [ 8 ]. CD47, also referred to as the “Do not-Eat-Me” signal, has received great attention in recent years and has been found to be overexpressed in most cancers [ 77 ]. CD47-blocking antibodies modified the accumulation of central lipid cores by improving the function of phagocytosis in mice with atherosclerosis [ 25 , 78 ].…”

Section: Therapeutic Approaches Targeting Immune and Inflammation mentioning

confidence: 99%

Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications

Wang

Liu

Shao

et al. 2020

Journal of Immunology Research

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Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a “from bench to bedside” perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

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“…In addition, a scenario in which cancer cells express MFG-E8 ( 41 ), NOX2 ( 42 ), PtdSer ( 21 ), in proximity to M2 macrophages ( 43 ) correlates with tumor aggressiveness. These observations suggest that phagocyte-homing in response to debris generated by tumor cells contributes to tumor-cell proliferation and may be heightened by the cytotoxic effects of anti-tumor therapies ( 44 ). Further, the promotion of tumor cell death by radiotherapy and chemotherapy can also lead to increased expression of efferocytic receptors such as Mertk ( 45 ) and TIM-4 ( 46 ).…”

Section: Efferocytosis In the Tme Promotes Tumor Progression And Metamentioning

confidence: 99%

LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness

et al. 2020

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One aim of cancer therapies is to induce apoptosis of tumor cells. Efficient removal of the apoptotic cells requires coordinated efforts between the processes of efferocytosis and LC3-associated phagocytosis (LAP). However, this activity has also been shown to produce anti-inflammatory and immunosuppressive signals that can be utilized by live tumor cells to evade immune defense mechanisms, resulting in tumor progression and aggressiveness. In the absence of LAP, mice exhibit suppressed tumor growth during efferocytosis, while LAP-sufficient mice show enhanced tumor progression. Little is known about how LAP or its regulators directly affect efferocytosis, tumor growth and treatment responses, and identifying the mechanisms involved has the potential to lead to the discovery of novel approaches to target cancer cells. Also incompletely understood is the direct effect of apoptotic cancer cells on LAP. This is particularly important as induction of apoptosis by current cytotoxic cancer therapies can potentially stimulate LAP following efferocytosis. Herein, we highlight the current understanding of the role of LAP and its relationship with efferocytosis in the tumor microenvironment with a view to presenting novel therapeutic strategies.

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Regulation of efferocytosis as a novel cancer therapy

Cited by 47 publications

References 143 publications

Macrophage‐Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention

Macrophage‐Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention

Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications

LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness

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