Targeting tumor-associated macrophages for cancer treatment

Li, Mengjun; He, Ling; Zhu, Jing; Zhang, Peng; Liang, Shufang

doi:10.1186/s13578-022-00823-5

Cited by 98 publications

(99 citation statements)

References 115 publications

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“…Novel anticancer TAM-targeting therapies are constantly being developed and improved, which are expected to break through traditional tumor-associated therapies and gain favorable clinical treatment results. Furthermore, a combination of TAM-targeting drugs with other anticancer drugs to get better efficacy will be an irresistible trend [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Hsp70–Bag3 Module Regulates Macrophage Motility and Tumor Infiltration via Transcription Factor LITAF and CSF1

Avinery

Gahramanov

Hesin

et al. 2022

Cancers

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The molecular chaperone Hsp70 has been implicated in multiple stages of cancer development. In these processes, a co-chaperone Bag3 links Hsp70 with signaling pathways that control cancer development. Recently, we showed that besides affecting cancer cells, Hsp70 can also regulate the motility of macrophages and their tumor infiltration. However, the mechanisms of these effects have not been explored. Here, we demonstrated that the Hsp70-bound co-chaperone Bag3 associates with a transcription factor LITAF that can regulate the expression of inflammatory cytokines and chemokines in macrophages. Via this interaction, the Hsp70–Bag3 complex regulates expression levels of LITAF by controlling its proteasome-dependent and chaperone-mediated autophagy-dependent degradation. In turn, LITAF regulates the expression of the major chemokine CSF1, and adding this chemokine to the culture medium reversed the effects of Bag3 or LITAF silencing on the macrophage motility. Together, these findings uncover the Hsp70–Bag3–LITAF–CSF1 pathway that controls macrophage motility and tumor infiltration.

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Section: Discussionmentioning

confidence: 99%

Hsp70–Bag3 Module Regulates Macrophage Motility and Tumor Infiltration via Transcription Factor LITAF and CSF1

Avinery

Gahramanov

Hesin

et al. 2022

Cancers

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“…Moreover, for patients with ovarian cancer, VEGFA in serum is expected to replace CA125 and become a molecular marker for the early diagnosis of ovarian cancer ( Maryam et al, 2021 ). Since M2 macrophages play an important role in tumor development and are associated with poor clinical outcomes ( Li et al, 2022 ), TNFa may promote the development of NPC by recruiting M2 macrophage infiltration ( Mardhiyah et al, 2021 ). IL6 is a cytokine that can interfere with the occurrence and development of tumors by activating downstream signal pathways.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations

et al. 2022

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Background: Celastrol, an important extract of Tripterygium wilfordii, shows strong antitumor activity in a variety of tumors including nasopharyngeal carcinoma (NPC). However, little is known about its targets in NPC. We aimed to screen the key gene targets of Celastrol in the treatment of NPC by means of in silico analyses (including network pharmacology and molecular docking) and experimental evaluations.Methods: The main target genes of Celastrol and the genes related to NPC were obtained by retrieving the relevant biological databases, and the common targets were screened. Protein-protein interaction analysis was used to screen the hub genes. Then, a “compound-target-disease” network model was created and molecular docking was used to predict the binding of Celastrol to the candidate hub proteins. Afterward, the expression changes of the candidate genes under the administration of Celastrol were verified in vitro and in vivo.Results: Sixty genes common to Celastrol and NPC were screened out, which may be related to numerous biological processes such as cell proliferation, apoptosis, and tube development, and enriched in various pathways such as PI3K- Akt, EGFR tyrosine kinase inhibitor resistance, and Apoptosis. The tight binding ability of the candidate hub proteins (TNF, VEGFA, and IL6) to Celastrol was predicted by molecular docking [Docking energy: TNF, −6.08; VEGFA,−6.76; IL6,−6.91(kcal/mol)]. In vitro experiments showed that the expression of TNF and VEGFA decreased while the expression of IL6 increased in NPC cells (CNE2 and HONE1) treated with Celastrol. In vivo experiments suggested that Celastrol significantly reduced the weight and volume of the transplanted tumors in tumor-bearing mice in vivo. The expression of TNF, VEGFA, and IL6 in the transplanted tumor cells could be regulated by using Celastrol, and the expression trends were consistent with the in vitro model.Conclusion: Several gene targets have been filtered out as the core targets of Celastrol in the treatment of NPC, which might be involved in a variety of signaling pathways. Hence, Celastrol may exert its anti-NPC activity through multiple targets and multiple pathways, which will provide new clues for further research. Future experiments are warranted to validate the findings.

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“…In the TME tumor-associated macrophages (TAMs) are abundant within stromal cells. TAMs are classified into two major subsets, M1-like and M2-like TAMs [ 46 ]. M1-like TAMs are activated by IFN-γ, TLRs, lipopolysaccharide and GM-CSF.…”

Section: The Tumor Microenvironmentmentioning

confidence: 99%

“…They enhance a T-helper 2 response and participate in the regression of inflammation and wound healing by secreting anti-inflammatory factors such as IL-10 and TGF-ß. M1-like TAMs secreting pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, IL-12 and IL-23 have anticancer effects, while M2-like TAMs contribute to tumor progression [ 46 ].…”

Section: The Tumor Microenvironmentmentioning

confidence: 99%

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy

Schirrmacher¹,

Gool²,

Stuecker³

2022

IJMS

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An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as “concomitant immunity” suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression. This review updates latest information about immunosuppression by the TME and discusses mechanisms of how oncolytic viruses, in particular NDV, and cellular immunotherapy can counteract the immunosuppressive effect of the TME. With regard to cellular immunotherapy, the review presents pre-clinical studies of post-operative active-specific immunotherapy and of adoptive T cell-mediated therapy in immunocompetent mice. Memory T cell (MTC) transfer in tumor challenged T cell-deficient nu/nu mice demonstrates longevity and functionality of these cells. Graft-versus-leukemia (GvL) studies in mice demonstrate complete remission of late-stage disease including metastases and cachexia. T cell based immunotherapy studies with human cells in human tumor xenotransplanted NOD/SCID mice demonstrate superiority of bone marrow-derived as compared to blood-derived MTCs. Results from clinical studies presented include vaccination studies using two different types of NDV-modified cancer vaccine and a pilot adoptive T-cell mediated therapy study using re-activated bone marrow-derived cancer-reactive MTCs. As an example for what can be expected from clinical immunotherapy against tumors with an immunosuppressive TME, results from vaccination studies are presented from the aggressive brain tumor glioblastoma multiforme. The last decades of basic research in virology, oncology and immunology can be considered as a success story. Based on discoveries of these research areas, translational research and clinical studies have changed the way of treatment of cancer by introducing and including immunotherapy.

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Targeting tumor-associated macrophages for cancer treatment

Cited by 98 publications

References 115 publications

Hsp70–Bag3 Module Regulates Macrophage Motility and Tumor Infiltration via Transcription Factor LITAF and CSF1

Hsp70–Bag3 Module Regulates Macrophage Motility and Tumor Infiltration via Transcription Factor LITAF and CSF1

Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy

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