Heme catabolism by tumor-associated macrophages controls metastasis formation

Consonni, Francesca Maria; Bleve, Augusto; Totaro, Maria Grazia; Storto, Mariangela; Kunderfranco, Paolo; Termanini, Alberto; Pasqualini, Fabio; Alì, Chiara; Pandolfo, Chiara; Sgambelluri, Francesco; Grazia, Giulia; Santinami, M.; Maurichi, Andrea; Milione, Massimo; Erreni, Marco; Doni, Andrea; Fabbri, Marco; Gribaldo, Laura; Rulli, Eliana; Soares, Miguel P.; Torri, Valter; Mortarini, Roberta; Anichini, Andrea; Sica, Antonio

doi:10.1038/s41590-021-00921-5

Cited by 84 publications

(72 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, he described a subset of TAM (F4/80 high ) which overexpress HO-1 (heme-oxygenase-1) that plays a critical role in promoting tumor metastasis and immunosuppression. Interestingly, in metastatic melanoma patients, HO-1 expression on various monocyte populations discriminates survival as a good prognostic marker in case of low expression (30). To conclude, HO-1 + myeloid cells represent a new prognostic indicator and a novel antimetastatic target.…”

Section: Session 4 -Tissue Microenvironmentmentioning

confidence: 86%

24th “Nantes Actualités en Transplantation” and 4th “LabEx Immunotherapy-Graft-Oncology” NAT and IGO Joint Meeting “New Horizons in Immunotherapy”

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Session 4 -Tissue Microenvironmentmentioning

confidence: 86%

24th “Nantes Actualités en Transplantation” and 4th “LabEx Immunotherapy-Graft-Oncology” NAT and IGO Joint Meeting “New Horizons in Immunotherapy”

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Interestingly, RORC1 induces C/EBPβ to sustain myeloid-derived suppressor cell expansion [22]. More recently, a new population of prometastatic TAMs, endowed with high rate of heme catabolism, was shown to be induced by an M-CSF-dependent activation of the transcription factor Nrf2 [23]. Therefore, in order to obtain a more comprehensive understanding of myeloid evolution in cancer carriers, we cannot ignore the integration of multistep mechanisms that alter the commitment of hematopoietic progenitors, their mobilization towards the periphery and the subsequent infiltration of tumors that expose myeloid cells to tumor-derived factors (TDFs) [8].…”

Section: Emergency Myelopoiesismentioning

confidence: 99%

“…Evidence has been also provided that the hematopoietic-specific phospholipase C (PLC)-β2 lipolytic enzyme promotes the mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention [27]. Complement component 3a receptor 1 (C3aR1) antagonists restrained neutrophil mobilization, and melanoma-bearing C3aR1-deficient mice had reduced tumor growth and frequency of heme oxygenase 1 (HO-1) expressing monocytic blood precursors of HO-1 + TAMs [23,28]. Blocking the C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) pathway is also a rational approach to inhibit the accumulation of M-MDSCs and TAMs in the TME and to limit the mobilization of bone marrow monocytes into the blood stream, since the activation of CCR2 attenuates the CXCR4 anchoring signaling [29,30].…”

Section: Myeloid Cells Mobilizationmentioning

confidence: 99%

Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective

Bleve

Consonni

Porta

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

In recent years, the immune system has emerged as a critical regulator of tumor development, progression and dissemination. Advanced therapeutic approaches targeting immune cells are currently under clinical use and improvement for the treatment of patients affected by advanced malignancies. Among these, anti-PD1/PD-L1 and anti-CTLA4 immune checkpoint inhibitors (ICIs) are the most effective immunotherapeutic drugs at present. In spite of these advances, great variability in responses to therapy exists among patients, probably due to the heterogeneity of both cancer cells and immune responses, which manifest in diverse forms in the tumor microenvironment (TME). The variability of the immune profile within TME and its prognostic significance largely depend on the frequency of the infiltrating myeloid cells, which often represent the predominant population, characterized by high phenotypic heterogeneity. The generation of heterogeneous myeloid populations endowed with tumor-promoting activities is typically promoted by growing tumors, indicating the sequential levels of myeloid reprogramming as possible antitumor targets. This work reviews the current knowledge on the events governing protumoral myelopoiesis, analyzing the mechanisms that drive the expansion of major myeloid subsets, as well as their functional properties, and highlighting recent translational strategies for clinical developments.

show abstract

“…This population, activated by Nrf2, localizes in tumor lesions, a signal that is coordinated by p50 NF-κB-CSF-R1-C3aR axis. This promotes more HO-1 expression, immunosuppression, and therefore lower survival rate of melanoma patients [67].…”

Section: Paradoxical Roles Of Ho-1 In Cancermentioning

confidence: 99%

An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases

Wang

Ashrafi

Modareszadeh

et al. 2021

Cancers

View full text Add to dashboard Cite

Heme is an essential prosthetic group in proteins and enzymes involved in oxygen utilization and metabolism. Heme also plays versatile and fascinating roles in regulating fundamental biological processes, ranging from aerobic respiration to drug metabolism. Increasing experimental and epidemiological data have shown that altered heme homeostasis accelerates the development and progression of common diseases, including various cancers, diabetes, vascular diseases, and Alzheimer’s disease. The effects of heme on the pathogenesis of these diseases may be mediated via its action on various cellular signaling and regulatory proteins, as well as its function in cellular bioenergetics, specifically, oxidative phosphorylation (OXPHOS). Elevated heme levels in cancer cells intensify OXPHOS, leading to higher ATP generation and fueling tumorigenic functions. In contrast, lowered heme levels in neurons may reduce OXPHOS, leading to defects in bioenergetics and causing neurological deficits. Further, heme has been shown to modulate the activities of diverse cellular proteins influencing disease pathogenesis. These include BTB and CNC homology 1 (BACH1), tumor suppressor P53 protein, progesterone receptor membrane component 1 protein (PGRMC1), cystathionine-β-synthase (CBS), soluble guanylate cyclase (sGC), and nitric oxide synthases (NOS). This review provides an in-depth analysis of heme function in influencing diverse molecular and cellular processes germane to disease pathogenesis and the modes by which heme modulates the activities of cellular proteins involved in the development of cancer and other common diseases.

show abstract

Heme catabolism by tumor-associated macrophages controls metastasis formation

Cited by 84 publications

References 51 publications

24th “Nantes Actualités en Transplantation” and 4th “LabEx Immunotherapy-Graft-Oncology” NAT and IGO Joint Meeting “New Horizons in Immunotherapy”

24th “Nantes Actualités en Transplantation” and 4th “LabEx Immunotherapy-Graft-Oncology” NAT and IGO Joint Meeting “New Horizons in Immunotherapy”

Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective

An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases

Contact Info

Product

Resources

About