The role of iron metabolism in cancer therapy focusing on tumor‐associated macrophages

Dong, Di; Zhang, Gejing; Yang, Juhua; Zhao, Bin; Wang, Shenghang; Wang, Luyao; Zhang, Ge; Shang, Peng

doi:10.1002/jcp.27569

Cited by 24 publications

(15 citation statements)

References 117 publications

(183 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Macrophages play a major role in iron homeostasis by recycling iron from senescent and dying red blood cells (RBC) back into the circulation and different tissues in the body (Andrews, 1999;Ganz, 2012;Hubler et al, 2015). Additionally, macrophage polarization is closely associated with iron metabolism (Dong et al, 2019). Studies have shown that over 60% of iron metabolism-related genes are differentially expressed between the M1/M2 macrophage axis (Recalcati et al, 2010).…”

Section: Iron Metabolismmentioning

confidence: 99%

“…IONs on the other hand, have been broadly explored in preclinical and clinical studies in the past decade (Hu et al, 2018). IONs accumulation in macrophages increased intracellular iron levels, thus promoting the proinflammatory phenotype (Laskar et al, 2013;Dong et al, 2019). Ferumoxytol, an FDA-approved ION for the treatment of anemia, inhibited tumor growth and metastatic spread in a xenograft mouse model by shifting TAM polarization toward the M1-like phenotype (Zanganeh et al, 2016).…”

Section: Iron Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Friend or Foe? Recent Strategies to Target Myeloid Cells in Cancer

Chaib

Chauhan

Makowski

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The tumor microenvironment (TME) is a complex network of epithelial and stromal cells, wherein stromal components provide support to tumor cells during all stages of tumorigenesis. Among these stromal cell populations are myeloid cells, which are comprised mainly of tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC), and tumor-associated neutrophils (TAN). Myeloid cells play a major role in tumor growth through nurturing cancer stem cells by providing growth factors and metabolites, increasing angiogenesis, as well as promoting immune evasion through the creation of an immune-suppressive microenvironment. Immunosuppression in the TME is achieved by preventing critical anti-tumor immune responses by natural killer and T cells within the primary tumor and in metastatic niches. Therapeutic success in targeting myeloid cells in malignancies may prove to be an effective strategy to overcome chemotherapy and immunotherapy limitations. Current therapeutic approaches to target myeloid cells in various cancers include inhibition of their recruitment, alteration of function, or functional re-education to an antitumor phenotype to overcome immunosuppression. In this review, we describe strategies to target TAMs and MDSCs, consisting of single agent therapies, nanoparticle-targeted approaches and combination therapies including chemotherapy and immunotherapy. We also summarize recent molecular targets that are specific to myeloid cell populations in the TME, while providing a critical review of the limitations of current strategies aimed at targeting a single subtype of the myeloid cell compartment. The goal of this review is to provide the reader with an understanding of the critical role of myeloid cells in the TME and current therapeutic approaches including ongoing or recently completed clinical trials.

show abstract

Section: Iron Metabolismmentioning

confidence: 99%

Section: Iron Metabolismmentioning

confidence: 99%

Friend or Foe? Recent Strategies to Target Myeloid Cells in Cancer

Chaib

Chauhan

Makowski

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Cluster 1 patients with lower TMB had a better prognosis than those in the other two clusters. Previous studies have shown that iron plays a critical role in the reprogramming of the TME ( 18 , 25 ). The TME is abundant with a variety of leukocytes, of which macrophages dominate.…”

Section: Discussionmentioning

confidence: 99%

Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Iron is one of the essential trace elements in the human body. An increasing amount of evidence indicates that the imbalance of iron metabolism is related to the occurrence and development of cancer. Here, we obtained the gene expression and clinical data of sarcoma patients from TCGA and the GEO database. The prognostic value of iron metabolism-related genes (IMRGs) in patients with sarcoma and the relationship between these genes and the immune microenvironment were studied by comprehensive bioinformatics analyses. Two signatures based on IMRGs were generated for the overall survival (OS) and disease-free survival (DFS) of sarcoma patients. At 3, 5, and 7 years, the areas under the curve (AUCs) of the OS signature were 0.708, 0.713, and 0.688, respectively. The AUCs of the DFS signature at 3, 5, and 7 years were 0.717, 0.689, and 0.702, respectively. Kaplan–Meier survival analysis indicated that the prognosis of high-risk patients was worse than that of low-risk patients. In addition, immunological analysis showed that there were different patterns of immune cell infiltration among patients in different clusters. Finally, we constructed two nomograms that can be used to predict the OS and DFS of sarcoma patients. The C-index was 0.766 (95% CI: 0.697–0.835) and 0.763 (95% CI: 0.706–0.820) for the OS and DFS nomograms, respectively. Both the ROC curves and the calibration plots showed that the two nomograms have good predictive performance. In summary, we constructed two IMRG-based prognostic models that can effectively predict the OS and DFS of sarcoma patients.

show abstract

“…There are now three major TAM therapies: inhibiting macrophage recruitment, depleting TAM, and promoting TAM anti-tumor transformation. For example, by blocking the most common CCL-2 and CCR-2 signaling pathways, macrophages recruitment and in ltration can be decreased, and tumor development can be delayed [29] . Some mannose-modi ed nanoliposome carriers and PLGA nanoparticle carriers selectively target the highly expressed mannose receptor (CD206) in M2 macrophages, which can accurately destroy M2 macrophages while having a low unfavorable effect on the body [30][31] .…”

Section: Discussionmentioning

confidence: 99%

M2 Macrophages Secrete CXCL13 to Promote Renal Cell Carcinoma Migration, Invasion, and EMT

Xie¹,

Chen²,

Zhong³

et al. 2021

Preprint

View full text Add to dashboard Cite

Objective: M2 macrophages are associated with a poor prognosis in a variety of malignancies. There are, however, few relevant investigations in clear cell renal cell carcinoma (ccRCC).Methods: The expression of M2 macrophages in ccRCC tissues was first discovered using immunohistochemistry in this study. Then, M2 macrophages were created in vitro to see how they affected the proliferation, migration, invasion, and EMT of ccRCC cells. Using qPCR and prognostic analysis identifies important chemokine. Antibody neutralization tests confirmed the chemokine’s involvement and function. Pathway inhibitors confirmed the main pathway of M2 macrophages in ccRCC. Finally, qPCR and IHC were used to confirm the expression of chemokine receptors in ccRCC tissues.Results: The presence of M2 macrophages was linked to a poor outcome in ccRCC. M2 macrophages enhanced the proliferation, migration, invasion, and EMT of ccRCC lines in vitro. CXCL13 was identified as the main chemokine by prognostic analysis and qPCR tests. CXCL13 neutralizing antibodies can inhibit the stimulation of M2 macrophages in ccRCC lines’ proliferation, migration, invasion, and EMT. M2 macrophages and CXCL13 may activate the Akt pathway in ccRCC lines, and Akt inhibitors decrease ccRCC lines proliferation, migration, invasion, and EMT. CXCR5 expression is a poor prognostic factor for renal cell carcinoma, according to qPCR and immunohistochemistry. In vivo experiments further proved that CXCL13 secreted by M2 macrophages can promote tumor proliferation.Conclusion: M2 macrophages in the immunological milieu secrete CXCL13, which promotes ccRCC proliferation, migration, invasion, and EMT. Our findings contribute to a better understanding of the function of the tumor microenvironment in the incidence and progression of ccRCC, and they may point to novel therapeutic targets for ccRCC.

show abstract

The role of iron metabolism in cancer therapy focusing on tumor‐associated macrophages

Cited by 24 publications

References 117 publications

Friend or Foe? Recent Strategies to Target Myeloid Cells in Cancer

Friend or Foe? Recent Strategies to Target Myeloid Cells in Cancer

Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas

M2 Macrophages Secrete CXCL13 to Promote Renal Cell Carcinoma Migration, Invasion, and EMT

Contact Info

Product

Resources

About