CARs and beyond: tailoring macrophage-based cell therapeutics to combat solid malignancies

Abdin, Shifaa M.; Paasch, Daniela; Morgan, Michael; Lachmann, Nico

doi:10.1136/jitc-2021-002741

Cited by 27 publications

(12 citation statements)

References 89 publications

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“…The results demonstrated that most immune cells (T cell, B cell, and macrophages M1/M2) expressed at a higher level in the high-risk group than in the low-risk group. Tumor-associated macrophages are a new targeting strategy to boost anticancer therapy and a key player in TME regulation, where they have been demonstrated to promote tumor growth, angiogenesis, and metastasis ( Abdin et al, 2021 ). As a result, our findings may provide new sights for deep macrophages in HCC.…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Yang

Liu

2021

Front. Cell Dev. Biol.

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Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, and numerous studies have demonstrated that an inflammatory environment can induce normal cells to transform into cancerous.Methods: We integrated genomic data to comprehensively assess the association between pyroptosis and tumor microenvironment (TME) cell-infiltrating characteristics in HCC, as well as the potential molecular function and clinical significance of lncRNA.Results: The analysis of CNV alteration frequency displayed that CNV changes were common in 33 PRGs, and most were focused on copy number amplification. As a result of lasso regression analysis, nine differentially expressed lncRNAs (AL031985.3, NRAV, OSMR-AS1, AC073611.1, MKLN1-AS, AL137186.2, AL049840.4, MIR4435-2HG, and AL118511.1) were selected as independent prognosis factors of HCC patients. Patients at high risk have poorer survival than those in the low-risk group in training and testing cohorts. A low-risk score was significantly associated with an IC50 of chemotherapeutics such as bortezomib (p < 0.001), but a high-risk score was significantly linked to docetaxel (p < 0.001), implying that signature served as a prospective predictor for chemosensitivity.Conclusion: This work suggests pyroptosis-related lncRNAs features and their potential mechanisms on tumor microenvironment. The exploration may assist in identifying novel biomarkers and assist patients in predicting their prognosis, clinical diagnosis, and management.

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Section: Resultsmentioning

confidence: 99%

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Yang

Liu

2021

Front. Cell Dev. Biol.

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“…CAR-T cell therapy has demonstrated promising efficacy in hematologic malignancies, while its potential application in solid tumors is challenging [ 240 ]. Researchers are investigating other immune cells as possible CAR platforms to deal with the limitations of CAR T cells [ 241 , 242 ]. CAR expression in macrophages plays an essential role in enhancing phagocytosis, polarizing the M2 phenotype to the M1 phenotype, and stimulating the anti-tumor activity of T cells.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

et al. 2022

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Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients are refractory or resistant to these therapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. Immunosuppressive cells such as myeloid-derived suppressive cells, tumor-associated macrophages, tumor-associated neutrophils, regulatory T cells (Tregs), and tumor-associated dendritic cells are critical factors correlated with immune resistance. In addition, cytokines and factors secreted by tumor cells or these immunosuppressive cells also mediate the tumor progression and immune escape of cancers. Thus, targeting these immunosuppressive cells and the related signals is the promising therapy to improve the efficacy of immunotherapies and reverse the immune resistance. However, even with certain success in preclinical studies or in some specific types of cancer, large perspectives are unknown for these immunosuppressive cells, and the related therapies have undesirable outcomes for clinical patients. In this review, we comprehensively summarized the phenotype, function, and potential therapeutic targets of these immunosuppressive cells in the tumor microenvironment.

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“…Indeed, targeting relevant metabolic pathways could allow reprogramming of macrophage polarization and thus improve the disease. In addition, macrophages themselves are more and more considered as potential therapeutic agents, for example as chimeric antigen receptor (CAR)-macrophages targeting and phagocytosing tumor cells ( 20 , 21 ). Combinations of such therapeutic macrophages with metabolic drugs aimed at modulating their phenotype could be powerful tools in a wide range of diseases.…”

Section: Discussionmentioning

confidence: 99%

Perspective on direction of control: Cellular metabolism and macrophage polarization

et al. 2022

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Macrophages are innate immune cells with high phenotypic plasticity. Depending on the microenvironmental cues they receive, they polarize on a spectrum with extremes being pro- or anti-inflammatory. As well as responses to microenvironmental cues, cellular metabolism is increasingly recognized as a key factor influencing macrophage function. While pro-inflammatory macrophages mostly use glycolysis to meet their energetic needs, anti-inflammatory macrophages heavily rely on mitochondrial respiration. The relationship between macrophage phenotype and macrophage metabolism is well established, however its precise directionality is still under question. Indeed, whether cellular metabolism per se influences macrophage phenotype or whether macrophage polarization dictates metabolic activity is an area of active research. In this short perspective article, we sought to shed light on this area. By modulating several metabolic pathways in bone marrow-derived macrophages, we show that disruption of cellular metabolism does per se influence cytokine secretion profile and expression of key inflammatory genes. Only some pathways seem to be involved in these processes, highlighting the need for specific metabolic functions in the regulation of macrophage phenotype. We thus demonstrate that the intact nature of cellular metabolism influences macrophage phenotype and function, addressing the directionality between these two aspects of macrophage biology.

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CARs and beyond: tailoring macrophage-based cell therapeutics to combat solid malignancies

Cited by 27 publications

References 89 publications

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma

Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

Perspective on direction of control: Cellular metabolism and macrophage polarization

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