Tumor-associated macrophages modulate angiogenesis and tumor growth in a xenograft mouse model of multiple myeloma

Sun, Menghong; Xiao, Qiankun; Wang, Xiaoqian; Yang, Chenbo; Chen, Chao; Tian, Xiangyu; Wang, Shuaiyuan; Li, Hui; Qiu, Sen; Shu, Jiao; Shou, Yuwei; Liang, Yinghao; Xue, Tong; Chen, Kuisheng

doi:10.1016/j.leukres.2021.106709

Cited by 11 publications

(10 citation statements)

References 29 publications

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“…Reduced blood vessel density and VEGF expression levels were observed in myeloma xenografts injected with M2-polarized macrophages and treated with the macrophage-depleting agent clodronate. In contrast, xenografts in untreated mice showed enhanced tumor growth and increased VEGF blood concentrations (62). In line with these findings, transcriptomic profiling of the immune cell compartment in patients suffering from refractory or relapsed myeloma, revealed enrichment of a distinct subset of macrophages expressing genes linked to angiogenesis such as VEGF-A or diphtheria toxin receptor (Heparin-Binding EGF-Like Growth Factor) (63).…”

Section: Tumor-associated Macrophagessupporting

confidence: 57%

Molecular Impact of the Tumor Microenvironment on Multiple Myeloma Dissemination and Extramedullary Disease

Förster

Radpour

2022

Front. Oncol.

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Multiple myeloma (MM) is the most common malignant monoclonal disease of plasma cells. Aside from classical chemotherapy and glucocorticoids, proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are used in the current treatment scheme of MM. The tumor microenvironment (TME) plays a fundamental role in the development and progression of numerous solid and non-solid cancer entities. In MM, the survival and expansion of malignant plasma cell clones heavily depends on various direct and indirect signaling pathways provided by the surrounding bone marrow (BM) niche. In a number of MM patients, single plasma cell clones lose their BM dependency and are capable to engraft at distant body sites or organs. The resulting condition is defined as an extramedullary myeloma (EMM). EMMs are highly aggressive disease stages linked to a dismal prognosis. Emerging literature demonstrates that the dynamic interactions between the TME and malignant plasma cells affect myeloma dissemination. In this review, we aim to summarize how the cellular and non-cellular BM compartments can promote plasma cells to exit their BM niche and metastasize to distant intra-or extramedullary locations. In addition, we list selected therapy concepts that directly target the TME with the potential to prevent myeloma spread.

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Section: Tumor-associated Macrophagessupporting

confidence: 57%

Molecular Impact of the Tumor Microenvironment on Multiple Myeloma Dissemination and Extramedullary Disease

Förster

Radpour

2022

Front. Oncol.

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“…Subsequent studies [ 43 , 44 ] have confirmed the positive association between M2 macrophage abundances in primary tumors and cancer metastasis in clinical sample tissues. Similar to what was determined from association studies utilizing clinical specimens, this tumor-promoting activity of M2 macrophages has also been underpinned by experiments using genetically modified mice [ 45 ] as well as in nude mice xenografted with tumor cells [ 46 ].…”

Section: Prognostic Significance Of M2 Macrophages In the Tumor Micro...mentioning

confidence: 84%

Small Tweaks, Major Changes: Post-Translational Modifications That Occur within M2 Macrophages in the Tumor Microenvironment

Liang

Tan

et al. 2022

Cancers

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The majority of proteins are subjected to post-translational modifications (PTMs), regardless of whether they occur in or after biosynthesis of the protein. Capable of altering the physical and chemical properties and functions of proteins, PTMs are thus crucial. By fostering the proliferation, migration, and invasion of cancer cells with which they communicate in the tumor microenvironment (TME), M2 macrophages have emerged as key cellular players in the TME. Furthermore, growing evidence illustrates that PTMs can occur in M2 macrophages as well, possibly participating in molding the multifaceted characteristics and physiological behaviors in the TME. Hence, there is a need to review the PTMs that have been reported to occur within M2 macrophages. Although there are several reviews available regarding the roles of M2 macrophages, the majority of these reviews overlooked PTMs occurring within M2 macrophages. Considering this, in this review, we provide a review focusing on the advancement of PTMs that have been reported to take place within M2 macrophages, mainly in the TME, to better understand the performance of M2 macrophages in the tumor microenvironment. Incidentally, we also briefly cover the advances in developing inhibitors that target PTMs and the application of artificial intelligence (AI) in the prediction and analysis of PTMs at the end of the review.

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“…Therefore, TAMs can exert an important function in the inflammatory response of the tumor microenvironment. For example, they can secrete a variety of cytokines, modulates angiogenesis, inhibit the immune function of T cells, and even promote tumor occurrence, development, metastasis, and deterioration 34 . CSF1 is a tumor‐promoting cytokine, with the participation of tumor cells, it binds to CSF1R of macrophages, attracts macrophages to the tumor area, and further accelerates the production of TAMs.…”

Section: Discussionmentioning

confidence: 99%

“…For example, they can secrete a variety of cytokines, modulates angiogenesis, inhibit the immune function of T cells, and even promote tumor occurrence, development, metastasis, and deterioration. 34 CSF1 is a tumor‐promoting cytokine, with the participation of tumor cells, it binds to CSF1R of macrophages, attracts macrophages to the tumor area, and further accelerates the production of TAMs. High expression of PD‐L1 on TAMs combined with PD‐1 on CD8 + T cells in the tumor microenvironment restrains the effect of CTL and participates in MM immune evasion (Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma

et al. 2022

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Background: Tumor-associated macrophages (TAMs) are originated from circulating mononuclear cells in peripheral blood. They result from the recruitment of tumor cells and are a vital constituent of the tumor microenvironment. TAMs may be involved in the immunological escape of vicious clonal plasma cells (PC) in the bone marrow (BM) of sufferers with myeloma.Methods: From March 2020 to January 2021, 28 healthy controls (HC) and 86 multiple myeloma (MM) (53 newly diagnosed MM [NDMM] and 33 remissions) patients were enrolled as objects of the study. The expression of TAMs in the BM, CSF1 on CD138 + cells, and CSF1R on macrophages were detected by the method of flow cytometry, and the expression of PD-1 on CD8 + T cells and PD-L1 on TAMs were also done. Bone marrow mononuclear cells (BMMNCs) were extracted and cultured into TAMs, CD8 + T cells were sorted by magnetic beads and cultured, a coculture system was established and different inhibitors were added.The expression of the perforin and granzyme B was detected by flow cytometry. Results:The percentage of TAMs in NDMM group (61.49 ± 2.176%) increased when compared with remission (23.08 ± 1.699%, p < 0.001) and HC group (17.95 ± 1.865%, p < 0.001), and TAMs decreased after adding CSF1R inhibitor.Moreover, the expression of CSF1 on CD138 + cells increased significantly in NDMM group (17.090 ± 0.9156%) than remission (8.214 ± 0.5911% p < 0.001), and HC group (5.257 ± 0.6231%, p < 0.001), and CSF1R on macrophages increased significantly in NDMM group (58.78 ± 2.286%) than remission (20.74 ± 1.376%, p < 0.001) and HC group (17.42 ± 1.081%, p < 0.001). The expression of PD-1 on CD8 + T cells in NDMM group (32.64 ± 2.982%) increased than remission (20.35 ± 2.335% p < 0.01) and HC group (17.53 ± 1.349%, p < 0.001), and PD-L1 on TAMs also increased in NDMM group (50.92 ± 2.554%) than remission (20.02 ± 1.893%, p < 0.001) and HC group (13.08 ± 1.289%, p < 0.001). When

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Tumor-associated macrophages modulate angiogenesis and tumor growth in a xenograft mouse model of multiple myeloma

Cited by 11 publications

References 29 publications

Molecular Impact of the Tumor Microenvironment on Multiple Myeloma Dissemination and Extramedullary Disease

Molecular Impact of the Tumor Microenvironment on Multiple Myeloma Dissemination and Extramedullary Disease

Small Tweaks, Major Changes: Post-Translational Modifications That Occur within M2 Macrophages in the Tumor Microenvironment

Tumor‐associated macrophages regulate the function of cytotoxic T lymphocyte through PD‐1/PD‐L1 pathway in multiple myeloma

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