Targeting tumor-associated macrophages for cancer immunotherapy

Shu, Yongheng; Cheng, Ping

doi:10.1016/j.bbcan.2020.188434

Cited by 92 publications

(89 citation statements)

References 119 publications

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“…Previous studies have shown that TAMs may promote tumor initiation through the induction of angiogenesis and thus exert an effect on prognosis. 33,34 Supporting this idea, we found that CD163+ cell density significantly correlated with CD34 expression in tumor tissues. These results suggest that TAMs may affect patient outcome in part by inducing CD34 expression in CB tissues.…”

supporting

confidence: 52%

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy

Zheng¹,

Yang²,

Huang³

et al. 2021

JIR

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Objective: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients. Methods: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features. Results: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan-Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68 + cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance. Conclusion: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.

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supporting

confidence: 52%

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy

Zheng¹,

Yang²,

Huang³

et al. 2021

JIR

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“…In addition, tumor cells have been reported to induce M2-like differentiation of macrophages to reduce immune attack by secretion of the cytokines IL-4, IL-10, and M-CSF [61][62][63]. Macrophages, called Kuper cells in the liver, inhibit the early development of hepatocellular carcinoma; However, during tumor progression, M1 switch to M2, leading to adaptive immune system suppression and tumor support [64,65]. Furthermore, M2 macrophages promote tumor progression and metastasis, and TAM in ltration is associated with poor prognosis in liver cancers [66].…”

Section: Discussionmentioning

confidence: 99%

Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential in Hepatocellular Carcinoma

Tian

Xin

et al. 2020

Preprint

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Background: Currently, the treatment for advanced hepatocellular carcinoma (HCC) is extremely limited. Ginsenoside Rg3, ganoderma lucidum polysaccharide, and Oridonin have shown great potential in anti-tumor therapy in previous studies, but low bioavailability and poor solubility seriously hinder their clinical application. Hence, new strategy for liver cancer are urgently needed. Methods: Cell viability, cell proliferation, cell migration, colony formation, tubule formation, sphere formation, and flow cytometry were used to assess the effect of a new drug, RGO-SMEDDS, (self-microemulsifying drug delivery system comprising of Rg3, ganoderma lucidum polysaccharide, and Oridonin) on HCC. Specific anti-tumor mechanisms of RGO-SMEDDS were investigated by western blot, qRT-PCR, and immunohistochemistry. Xenografts and staining with hematoxylin and eosin were used to assess the effects of RGO-SMEDDS on tumorigenesis in vivo.Results: We developed a self-microemulsifying drug delivery system (RGO-SMEDDS) for these three plant monomers. Treatment with RGO-SMEDDS resulted in induction of G2/M phase arrest and apoptosis, inhibition of migration and invasion, and suppression of cell proliferation, both in vitro and in vivo. Furthermore, RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by down-regulation of vascular endothelial growth factor and its receptor, and attenuated stemness of HCC by inhibiting EGFR/AKT/GSK-3α/β signaling pathways. In addition to excellent anti-tumor effects, RGO-SMEDDS showed considerable safety in acute toxicity tests.Conclusion: RGO-SMEDDS exerted significant anti-tumor effects by reducing angiogenesis, remodeling immune microenvironments, and promoting apoptosis, without obvious toxicities. With these attributes RGO-SMEDDS is a promising therapy for the treatment of hepatocellular carcinoma.

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“…As can be seen from the literature review, a wide range of therapeutic measures inspired by TAM targeting are under research and development. Significantly, the TAM targeting measure may lead to even better outcomes when combined with other therapies like radiotherapies and chemotherapies [28,136,140,165]. Considering the therapy resistance or side effects of radiotherapies and chemotherapies, the TAM-mediated treatment strategies will open a novel avenue of well-adapted therapies.…”

Section: Tams Reprogrammingmentioning

confidence: 99%

“…Although TAMs have a profound influence on cancer progression, and thus have a become direct target in some cancer therapy measures [69], the execution of two general strategies, including the inhibition of TAM infiltration into the cancer environment (through recruitment prevention or physical depletion), and TAM reprogramming using pharmaceutical agents and approaches, are not completely flawless [167]. Although limited results may disappoint the agent's application, the high toxicity for non-cancer cells, and not enough specificity of drugs used for targeting TAMs, are being mentioned as serious side effects of TAM-based therapies [165]. Meanwhile, TAM targeting seems to be unable to eradicate cancer by itself and is toxic for patients at inordinate applications/dosages [178].…”

Section: Treatment Drawbacksmentioning

confidence: 99%

Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment

Moeini

Niedźwiedzka-Rystwej

2021

IJMS

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Macrophages are one of the most important cells of the innate immune system and are known for their ability to engulf and digest foreign substances, including cellular debris and tumor cells. They can convert into tumor-associated macrophages (TAMs) when mature macrophages are recruited into the tumor microenvironment. Their role in cancer progression, metastasis, and therapy failure is of special note. The aim of this review is to understand how the presence of TAMs are both advantageous and disadvantageous in the immune system.

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Targeting tumor-associated macrophages for cancer immunotherapy

Cited by 92 publications

References 119 publications

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy

Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential in Hepatocellular Carcinoma

Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment

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Targeting tumor-associated macrophages for cancer immunotherapy

Cited by 92 publications

References 119 publications

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy

Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential&nbsp;in Hepatocellular Carcinoma

Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment

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Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential in Hepatocellular Carcinoma