Shaping Polarization Of Tumor-Associated Macrophages In Cancer Immunotherapy

Gao, Jing; Liang, Yuanzheng; Wang, Liang

doi:10.3389/fimmu.2022.888713

Cited by 164 publications

(122 citation statements)

References 76 publications

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“…Due to the influence of cytokines in the TME, TAMs can be divided into two distinct polarized forms, M1 and M2 macrophages. The former is responsible for killing tumor cells; the latter is able to promote tumor growth (223). Macrophage M1/M2 polarization is adjustable and reversible.…”

Section: Regulation Of Macrophages By Adam17mentioning

confidence: 99%

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.

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Section: Regulation Of Macrophages By Adam17mentioning

confidence: 99%

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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“…ROCK regulating the phosphorylation of STAT3 to promote macrophage polarisation is not a new concept, and has previously been reported in chronic graft versus host disease, hepatocellular carcinoma and breast cancer. 88 , 89 , 90 To investigate the mechanism by which ROCK regulates macrophage polarisation, we elevated the phosphorylation of STAT3 in bleomycin‐ and radiation‐induced PF cells treated with WXWH0265, a ROCK inhibitor. The phosphorylation of STAT3 was inhibited by the decrease in M2 macrophage polarisation after WXWH0265 treatment, which verified our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ROCK ameliorates pulmonary fibrosis by suppressing M2 macrophage polarisation through phosphorylation of STAT3

Cheng

Zhang

et al. 2022

Clinical & Translational Med

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Background Emerging evidence provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), and rare anti‐PF therapeutic method has promising effect in its treatment. Rho‐associated coiled‐coil kinases (ROCK) inhibition significantly ameliorates bleomycin‐induced PF and decreases macrophage infiltration, but the mechanism remains unclear. We established bleomycin and radiation‐induced PF to identify the activity of WXWH0265, a newly designed unselective ROCK inhibitor in regulating macrophages. Methods Bleomycin‐induced PF was induced by intratracheal instillation and radiation‐induced PF was induced by bilateral thoracic irradiation. Histopathological techniques (haematoxylin and eosin, Masson's trichrome and immunohistochemistry) and hydroxyproline were used to evaluate PF severity. Western blot, quantitative real‐time reverse transcription‐polymerase chain reaction and flow cytometry were performed to explore the underlying mechanisms. Bone marrow‐derived macrophages (BMDMs) were used to verify their therapeutic effect. Clodronate liposomes were applied to deplete macrophages and to identify the therapeutic effect of WXWH0265. Results Therapeutic administration of ROCK inhibitor ameliorates bleomycin‐induced PF by inhibiting M2 macrophages polarisation. ROCK inhibitor showed no significant anti‐fibrotic effect in macrophages‐depleted mice. Treatment with WXWH0265 demonstrated superior protection effect in bleomycin‐induced PF compared with positive drugs. In radiation‐induced PF, ROCK inhibitor effectively ameliorated PF. Fibroblasts co‐cultured with supernatant from various M2 macrophages phenotypes revealed that M2 macrophages stimulated by interleukin‐4 promoted extracellular matrix production. Polarisation of M2 macrophages was inhibited by ROCK inhibitor treatment in vitro. The p‐signal transducer and activator of transcription 3 (STAT3) in lung tissue and BMDMs was significantly decreased in PF in vivo and vitro after treated with ROCK inhibitors. Conclusion Inhibiting ROCK could significantly attenuate bleomycin‐ and radiation‐induced PF by regulating the macrophages polarisation via phosphorylation of STAT3. WXWH0265 is a kind of efficient unselective ROCK inhibitor in ameliorating PF. Furthermore, the results provide empirical evidence that ROCK inhibitor, WXWH0265 is a potential drug to prevent the development of PF.

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“…Tumor-associated macrophages (TAMs) in the tumor microenvironment are heterogeneous subsets, including M1 antitumor and M2 tumor-promoting phenotypes. TAMs primarily exert M2-like tumor-promoting effects in the TME and regulate various malignant effects, such as angiogenesis, immunosuppression, and tumor metastasis (33,34). Prior work has reported that each of M1 and M2 macrophages are produced by M0 is a quiescent state of macrophages with no particular role until they become polarized (35).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Cuproptosis-Related lncRNAs in Immune Infiltration and Prognosis in Hepatocellular Carcinoma

Liu¹,

Wu²,

Lai³

et al. 2022

Preprint

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Background Being among the most common malignancies worldwide, hepatocellular carcinoma (HCC) accounts now as the fourth primary reason for cancer death. The regulation of cell death is the most crucial step in tumor progression and has become a crucial target for nearly all therapeutic options. Cuproptosis is a lately discovered copper-dependent method of apoptosis regulation. However, its primary function in carcinogenesis is still unclear. Results We developed a signature consisted of four cuproptosis-related lncRNAs (AL133243.2, AL031985.3, AL137127.1, and SNHG18). Compared to the low-risk group, the high-risk group exhibited a poorer outcome. The cuproptosis-related lncRNA signature can estimate HCC patients’ fate independently. Tumorigenesis and immunological-related pathways were primarily enhanced in the high-risk group, as determined by GSEA. Immunotherapy and standard chemotherapy medications such as erlotinib and lapatinib were more suitable for low-risk patients, whereas sunitinib, paclitaxel, gemcitabine, and imatinib were more suitable for high-risk patients. Conclusion The prognostic signature may forecasting HCC patients’ prognosis and establishes the fundamental function of cuproptosis-related lncRNAs in HCC. Cuproptosis-related lncRNAs may perform an important part in the tumor immune microenvironment (TIME), making them a promising treatment for HCC patients.

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Shaping Polarization Of Tumor-Associated Macrophages In Cancer Immunotherapy

Cited by 164 publications

References 76 publications

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

Inhibition of ROCK ameliorates pulmonary fibrosis by suppressing M2 macrophage polarisation through phosphorylation of STAT3

Comprehensive Analysis of Cuproptosis-Related lncRNAs in Immune Infiltration and Prognosis in Hepatocellular Carcinoma

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