Targeting tumor associated macrophages (TAMs) via nanocarriers

Singh, Yuvraj; Pawar, Vivek K.; Meher, Jaya Gopal; Raval, Kavit; Kumar, Abdhesh; Shrivastava, Rahul; Bhadauria, Smrati; Chourasia, Manish K.

doi:10.1016/j.jconrel.2017.03.395

Cited by 110 publications

(60 citation statements)

References 177 publications

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“…M2-polarized macrophages are commonly called tumor-associated macrophages (TAMs), and these promote cancer cell growth, invasion, metastasis, and angiogenesis and are one of the primary tumor-infiltrating immune cells. Several lines of evidence suggest that TAMs not only open up avenues for the initiation and metastasis of tumor cells, but they also exhibit immunosuppressive activities and promote tumor angiogenesis [ 7 ]. Recent large longitudinal studies have reported that TAM infiltration in the tumor site frequently correlates with poor prognosis of various cancers [ 8 , 9 ] .…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling

Cui

Wei

et al. 2018

J Exp Clin Cancer Res

233

146

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BackgroundAccumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.MethodsHuman THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM–promoted tumor migration was detected using western blotting.ResultsHere we found that AS-IV significantly inhibited IL-13 and IL-4–induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM–induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.ConclusionsAS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV’s ability to inhibit the metastasis of lung cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0878-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling

Cui

Wei

et al. 2018

J Exp Clin Cancer Res

233

146

View full text Add to dashboard Cite

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“…We also hypothesized that targeted delivery of drugs to tumor‐associated macrophages could improve repolarization efficiency as compared to a nontargeted strategy. Recent studies have also pointed out the potential advantages of enhanced targeting of TAMs using monoclonal CD206 antibodies . Hence, we report the modular design of anti‐CD206 DNTs, which can preferentially target TAMs to achieve better repolarization.…”

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confidence: 95%

CSF1R‐ and SHP2‐Inhibitor‐Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor‐Associated Macrophages

et al. 2019

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Immune modulation of macrophages has emerged as an attractive approach for anti‐cancer therapy. However, there are two main challenges in successfully utilizing macrophages for immunotherapy. First, macrophage colony stimulating factor (MCSF) secreted by cancer cells binds to colony stimulating factor 1 receptor (CSF1‐R) on macrophages and in turn activates the downstream signaling pathway responsible for polarization of tumor‐associated macrophages (TAMs) to immunosuppressive M2 phenotype. Second, ligation of signal regulatory protein α (SIRPα) expressed on myeloid cells to CD47, a transmembrane protein overexpressed on cancer cells, activates the Src homology region 2 (SH2) domain ‐phosphatases SHP‐1 and SHP‐2 in macrophages. This results in activation of “eat‐me‐not” signaling pathway and inhibition of phagocytosis. Here, it is reported that self‐assembled dual‐inhibitor‐loaded nanoparticles (DNTs) target M2 macrophages and simultaneously inhibit CSF1R and SHP2 pathways. This results in efficient repolarization of M2 macrophages to an active M1 phenotype, and superior phagocytic capabilities as compared to individual drug treatments. Furthermore, suboptimal dose administration of DNTs in highly aggressive breast cancer and melanoma mouse models show enhanced anti‐tumor efficacy without any toxicity. These studies demonstrate that the concurrent inhibition of CSF1‐R and SHP2 signaling pathways for macrophage activation and phagocytosis enhancement could be an effective strategy for macrophage‐based immunotherapy.

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“…Current macrophage‐targeted therapies under development aim to: 1) inhibit monocyte/macrophage recruitment, 2) deplete macrophages, or 3) activate macrophage anti‐tumor functions ( Figure and Table 1 ). There exists some controversy about whether TAMs are derived from blood‐circulating monocytes or from infiltrating peripheral tissue macrophages . However, inhibiting monocyte recruitment and their subsequent maturation into TAMs by blocking the C‐C motif chemokine ligand 2 (CCL2)–C‐C motif chemokine receptor 2 (CCR2) axis has indeed improved survival in tumor‐bearing mice .…”

Section: Synthetic Biomaterials To Target Tams In Cancer By Systemic mentioning

confidence: 99%

Progress on Modulating Tumor‐Associated Macrophages with Biomaterials

2019

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Tumor‐associated macrophages (TAMs) are a complex and heterogeneous population of cells within the tumor microenvironment. In many tumor types, TAMs contribute toward tumor malignancy and are therefore a therapeutic target of interest. Here, three major strategies for regulating TAMs are highlighted, emphasizing the role of biomaterials in these approaches. First, systemic methods for targeting tumor‐associated macrophage are summarized and limitations to both passive and active targeting approaches considered. Second, lessons learned from the significant literature on wound healing and macrophage response to implanted biomaterials are discussed with the vision of applying these principles to localized, biomaterial‐based modulation of tumor‐associated macrophage. Finally, the developing field of engineered macrophages, including genetic engineering and integration with biomaterials or drug delivery systems, is examined. Analysis of major challenges in the field along with exciting opportunities for the future of macrophage‐based therapies in oncology are included.

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Targeting tumor associated macrophages (TAMs) via nanocarriers

Cited by 110 publications

References 177 publications

Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling

Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling

CSF1R‐ and SHP2‐Inhibitor‐Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor‐Associated Macrophages

Progress on Modulating Tumor‐Associated Macrophages with Biomaterials

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