Research trends in pharmacological modulation of tumor‐associated macrophages

Wang, Neng; Wang, Shengqi; Wang, Xuan; Zheng, Yifeng; Yang, Bowen; Zhang, Juping; Pan, Bo; Gao, Jian‐Li; Wang, Zhiyu

doi:10.1002/ctm2.288

Cited by 77 publications

(67 citation statements)

References 411 publications

(505 reference statements)

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“…Thus, blocking CSF-1 and CSF-1R-mediated signaling can be a promising strategy for cancer immunotherapy. Currently, several small molecules aimed at CSF-1/CSF-1R are being tested in clinical studies, including PLX3397/Pexidartinib, DCC-3014, BLZ945, FPA008/Cabiralizumab, and MCS110 ( 110 ). For instance, a study showed that PLX3397, an antagonist of CSF-1R, inhibited cell proliferation in gliomas and induced tumor regression via depletion of TAMs ( 111 ).…”

Section: Therapeutic Strategies Targeting Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

et al. 2021

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Macrophages, an important class of innate immune cells that maintain body homeostasis and ward off foreign pathogens, exhibit a high degree of plasticity and play a supportive role in different tissues and organs. Thus, dysfunction of macrophages may contribute to advancement of several diseases, including cancer. Macrophages within the tumor microenvironment are known as tumor-associated macrophages (TAMs), which typically promote cancer cell initiation and proliferation, accelerate angiogenesis, and tame anti-tumor immunity to promote tumor progression and metastasis. Massive infiltration of TAMs or enrichment of TAM-related markers usually indicates cancer progression and a poor prognosis, and consequently tumor immunotherapies targeting TAMs have gained significant attention. Here, we review the interaction between TAMs and cancer cells, discuss the origin, differentiation and phenotype of TAMs, and highlight the role of TAMs in pro-cancer functions such as tumor initiation and development, invasive metastasis, and immunosuppression. Finally, we review therapies targeting TAMs, which are very promising therapeutic strategies for malignant tumors.

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Section: Therapeutic Strategies Targeting Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

et al. 2021

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“…In the presence of T-helper 2 cell-type cytokines, M1 TAMs are polarized toward the M2 phenotype, which is immunosuppressive and promotes tumor growth [ 68 ]. In addition, the interaction of M2 TAMs with cancer cells and various non-cancer cells promotes cancer cell proliferation, drug resistance, and distant metastasis, attracting macrophages that form malignant feedback loops and continuously strengthen immunosuppression [ 69 ].…”

Section: Immunosuppressive Tmementioning

confidence: 99%

“…4 a) [ 70 ]. Another study showed that the polarization of M2 TAMs is mediated by multiple signaling pathways [ 69 ], especially PI3K-γ and CSF-1/CSF-1R. Therefore, a nanomicelle carrying an M2 TAM-targeting peptide was prepared to co-deliver the PI3K-γ inhibitor BEZ 235 and an siRNA silencing the colony stimulating factor-1 receptor (CSF-1R) in order to inhibit TAMs specifically [ 71 ].…”

Section: Immunosuppressive Tmementioning

confidence: 99%

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Jia

Zhang

et al. 2021

J Nanobiotechnol

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Pancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

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“…In general, these therapeutic options target different properties of TAMs such as their survival, polarization, recruitment, phagocytosis, and angiogenesis [ 168 ]. Different pharmacological techniques for TAMs such as targeting chemokine-chemokine receptors and tyrosine kinases, as well as the use of bisphosphonates and nanotechnology have been evaluated [ 169 ]. Table 3 lists the clinical trials of therapeutics being tested against TAMs in pancreatic cancer.…”

Section: Immune Characterization Of the Tme And Impact On The Ecmmentioning

confidence: 99%

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

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Research trends in pharmacological modulation of tumor‐associated macrophages

Abstract: The biofunctions and clinical implications of TAMs in cancer progression were summarized. • The current pharmaceutical targets in TAMs regulation were introduced and discussed.

Cited by 77 publications

References 411 publications

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

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