The complex role of tumor-infiltrating macrophages

Christofides, Anthos; Strauss, Laura; Yeo, Alan T.; Cao, Carol; Charest, Alain; Boussiotis, Vassiliki A.

doi:10.1038/s41590-022-01267-2

Cited by 390 publications

(210 citation statements)

References 118 publications

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“…The results demonstrate that macrophage M0 was signi cantly linked to the risk score, whereas the in ltration ratio of monocyte cells was adversely linked to this parameter. Macrophages are an old cell kind contributed in tissue homeostasis and pathogen ghting (32). Tumor-associated macrophages (TAMs) in the tumor microenvironment are heterogeneous subsets, including M1 antitumor and M2 tumor-promoting phenotypes.…”

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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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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show abstract

“…Inhibition of leukocyte immunoglobulin-like receptor subfamily B (LILRB)-MHCI pathway axis could recover the phagocytic capacity of TAMs (Barkal et al, 2018). Finally, CAR expressed by TAMs has been reported to improve phagocytosis, transform TAMs to the M1 phenotype, and enhance anti-tumor immunity (Christofides et al, 2022). CAR for phagocytosis (CAR-P) could improve the phagocytic capacity of TAMs and hinder tumor Frontiers in Genetics frontiersin.org cell growth in solid tumors (Morrissey et al, 2018;Kumari and Choi, 2022).…”

Section: The Tams-based Immunotherapiesmentioning

confidence: 99%

“…Macrophages have been traditionally divided into two types: inflammatory M1-macrophages (anti-tumoral phenotypes) and immunosuppressive M2-macrophages (pro-tumoral phenotypes) ( Cassetta and Pollard, 2020 ; Christofides et al, 2022 ). Macrophages are recruited into the tumor sites and play different functions, termed tumor-associated macrophages.…”

Section: Effector Phasementioning

confidence: 99%

“…Macrophages are recruited into the tumor sites and play different functions, termed tumor-associated macrophages. CSF1 is a key factor for the recruitment of macrophages and polarizes macrophages to express the M2 phenotype ( De et al, 2016 ; Christofides et al, 2022 ). It is reported that the inhibition of CSF-1 could decrease the accumulation of TAM and transform the M2 phenotype into the M1 phenotype ( Ramesh et al, 2019 ).…”

Section: Effector Phasementioning

confidence: 99%

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The soldiers needed to be awakened: Tumor-infiltrating immune cells

Wang

Zhuling³

et al. 2022

Front. Genet.

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In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

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“…The importance of the tumor microenvironment (TME) in tumorigenesis is being extensively explored ( 5 , 6 ). GC is a dynamic entity.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

Yang

Zou

et al. 2022

Front. Immunol.

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Although significant progress has been made in the study of gastric cancer (GC), clinicians lack reliable protein markers for accurate diagnosis and tumor stratification. Neutrophil extracellular traps (NETs) are networks of extracellular fibers composed of DNA from neutrophils. We have previously reported that abundant NETs are deposited in GC, damaging human umbilical vein endothelial cells (HUVECs) and triggering the release of tissue factors, leading to a hypercoagulable state in GC. However, the specific effects of NETs on HUVECs are unclear. We aimed to explore the functional changes caused by NETs on HUVECs, providing evidence that NETs may fuel GC progression. Through quantitative proteomics, we identified 6182 differentially expressed proteins in NET-stimulated HUVECs by TMT. The reliability of the TMT technique was confirmed by parallel reaction monitoring (PRM) analysis of 17 differentially expressed proteins. Through bioinformatics analysis, we found that NETs upregulate ANGPT2 in HUVECs. We comprehensively analyzed the prognosis, biological function, immune response, and therapeutic value of ANGPT2 in GC. We found that overexpression of ANGPT2 in GC is associated with poor prognosis and potentially regulates multiple biological functions. At the same time, ANGPT2 also predicted immunotherapeutic and chemotherapeutic responses in GC. In conclusion, NETs promoted ANGPT2 overexpression in the GC microenvironment. In the future, the neutrophil/NETs-ANGPT2 axis may provide a new target for the treatment of GC.

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The complex role of tumor-infiltrating macrophages

Cited by 390 publications

References 118 publications

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

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

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

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