C1q+ macrophages: passengers or drivers of cancer progression

Revel, Margot; Sautès-Fridman, Catheriné; Fridman, Wolf‐Herman; Roumenina, Lubka T.

doi:10.1016/j.trecan.2022.02.006

Cited by 71 publications

(62 citation statements)

References 57 publications

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“…Complement is an important part of the innate immune system, which plays a role in resisting pathogen invasion and protecting the host ( Roumenina et al, 2019a ). Although C1Q has been proved to promote cell death in most types of cancers, in some cancers, the role of C1Q is completely opposite, which leads to cancer progression ( Revel et al, 2022 ). In clear-cell renal cell carcinoma, tumour-associated macrophages generate C1r, C1s, C4, and C3, after being hijacked by cancer cells, and then initiates the classical pathway of the complement cascade of IgG immunity in tumour and promotes inflammation and T-cell exhaustion, leading to tumour progression ( Roumenina et al, 2019b ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Yang

Che

et al. 2022

Front. Genet.

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Background: Skin cutaneous melanoma (SKCM) is a common malignancy that is associated with increased morbidity and mortality. Complement C1Q is composed of C1QA, C1QB, and C1QC and is involved in the occurrence and development of many malignant tumours. However, the effect of C1QA, C1QB, and C1QC expression on tumour immunity and prognosis of cutaneous melanoma remains unclear.Methods: First, we analysed C1QA, C1QB, and C1QC expression levels and prognostic values using Gene Expression Profiling Interactive Analysis (GEPIA) and Tumour Immune Estimation Resource (TIMER) analysis, and further validation was performed using RT-qPCR, The Human Protein Atlas, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus dataset. We then performed univariate/multivariate Cox proportional hazard model, clinicopathological correlation, and receiver operating characteristic curve analysis using TCGA dataset and established a nomogram model. Differentially expressed genes associated with C1QA, C1QB, and C1QC in SKCM were identified and analysed using LinkedOmics, TIMER, the Search Tool for the Retrieval of Interacting Genes database, and Metascape and Cytoscape software platforms. We used TIMER, GEPIA, and single-sample gene set enrichment analysis (ssGSEA) to analyse the relationship between the three genes and the level of immune cell infiltration, biomarkers, and checkpoint expression in SKCM. Finally, GSEA was utilized to study the functional pathways of C1QA, C1QB, and C1QC enrichment in SKCM.Results: The overexpression of C1QA, C1QB, and C1QC provided significant value in the diagnosis of SKCM and has been associated with better overall survival (OS). Multivariate Cox regression analysis indicated that C1QA, C1QB, and C1QC are independent prognostic biomarkers for patients with SKCM. Immune cell infiltration, biomarkers, and checkpoints were positively correlated with the expression of C1QA, C1QB, and C1QC. Furthermore, the results of functional and pathway enrichment analysis showed that immune-related and apoptotic pathways were significantly enriched in the high-expression group of C1QA, C1QB, and C1QC.Conclusion: We found that C1QA, C1QB, and C1QC can be used as biomarkers for the diagnosis and prognosis of SKCM patients. The upregulated expression levels of these three complement components benefit patients from OS and may increase the effect of immunotherapy. This result may be due to the dual effects of anti-tumour immunity and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Yang

Che

et al. 2022

Front. Genet.

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“…Higher expression of C1q and high numbers of the C1q positive macrophages positively correlates with markers of T cell exhaustion (PD-1 and LAG3) and poor clinical outcome for systemic lupus erythematosus ( 101 ). Further, C1q + TAMs might be playing similar role in cancer by promoting T cell exhaustion and their tumor accumulation is often associated with poor prognosis ( 102 ). C1q is thought to interact with surface bound receptors on TAMs, in addition to controlling T cell metabolism via mitochondrial receptor engagement as described by Ling et al.…”

Section: Sites Of Complement Production and Activationmentioning

confidence: 99%

Inside-Out of Complement in Cancer

et al. 2022

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The role of complement in cancer has received increasing attention over the last decade. Recent studies provide compelling evidence that complement accelerates cancer progression. Despite the pivotal role of complement in fighting microbes, complement seems to suppress antitumor immunity via regulation of host cell in the tumor microenvironment. Although most studies link complement in cancer to complement activation in the extracellular space, the discovery of intracellular activation of complement, raises the question: what is the relevance of this process for malignancy? Intracellular activation is pivotal for the survival of immune cells. Therefore, complement can be important for tumor cell survival and growth regardless of the role in immunosuppression. On the other hand, because intracellular complement (the complosome) is indispensable for activation of T cells, these functions will be essential for priming antitumor T cell responses. Here, we review functions of complement in cancer with the consideration of extra and intracellular pathways of complement activation and spatial distribution of complement proteins in tumors and periphery and provide our take on potential significance of complement as biomarker and target for cancer therapy.

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“…C1r and C1s are produced by the liver, while C1q is produced primarily by adherent monocytes, tissue macrophages and immature dendritic cells, suggesting that at least a proportion of the C1 complexes is formed in the circulation [ 21 , 22 , 23 ]. Upon C1 complex formation, large parts of C1r and C1s are hidden within the cone of C1q collagen stalks.…”

Section: Resultsmentioning

confidence: 99%

Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus Nephritis

Radanova

Vasilev

Mihaylova

et al. 2022

IJMS

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Autoantibodies against the complement component C1q (anti-C1q) are among the main biomarkers in lupus nephritis (LN) known to contribute to renal injury. C1q, the recognition subcomponent of the complement classical pathway, forms a heterotetrameric complex with C1r and C1s, and can also associate a central complement regulator and C1 Inhibitor (C1-Inh). However, the frequency and the pathogenic relevance of anti-C1r, anti-C1s and anti-C1-Inh autoantibodies remain poorly studied in LN. In this paper, we screened for anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh autoantibodies and evaluated their association with disease activity and severity in 74 LN patients followed up for 5 years with a total of 266 plasma samples collected. The presence of anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh was assessed by ELISA. IgG was purified by Protein G from antigen-positive plasma and their binding to purified C1q, C1r and C1s was examined by surface plasmon resonance (SPR). The abilities of anti-C1q, anti-C1r and anti-C1s binding IgG on C1 complex formation were analyzed by ELISA. The screening of LN patients’ plasma revealed 14.9% anti-C1q positivity; only 4.2%, 6.9% and 0% were found to be positive for anti-C1r, anti-C1s and anti-C1-Inh, respectively. Significant correlations were found between anti-C1q and anti-dsDNA, and anti-nuclear antibodies, C3 and C4, respectively. High levels of anti-C1q antibodies were significantly associated with renal histologic lesions and correlated with histological activity index. Patients with the most severe disease (A class according to BILAG Renal score) had higher levels of anti-C1q antibodies. Anti-C1r and anti-C1s antibodies did not correlate with the clinical characteristics of the LN patients, did not interfere with the C1 complex formation, and were not measurable via SPR. In conclusion, the presence of anti-C1q, but not anti-C1s or anti-C1r, autoantibodies contribute to the autoimmune pathology and the severity of LN.

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C1q+ macrophages: passengers or drivers of cancer progression

Cited by 71 publications

References 57 publications

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Inside-Out of Complement in Cancer

Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus Nephritis

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