The Yin Yang of Complement and Cancer

Meri, Seppo; Magrini, Elena; Mantovani, Alberto; Garlanda, Cecilia

doi:10.1158/2326-6066.cir-23-0399

Cited by 4 publications

(2 citation statements)

References 105 publications

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“…Notably, while traditionally considered protective, complement activation can also accelerate tumor progression through mediators such as C3a and C5a. These anaphylatoxins contribute to chronic inflammation, angiogenesis, and metastasis, presenting potential targets for cancer biomarkers and therapeutic interventions (Bouwens van der Vlis et al 2018 )(Meri et al 2023 ). Our analyses via GO, KEGG, and GSEA identified DNAJC1’s involvement in extracellular matrix organization and collagen binding within the GBM TME.…”

Section: Discussionmentioning

confidence: 99%

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration

Zhang,

Zheng,

Chen

et al. 2024

J Cancer Res Clin Oncol

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Background Glioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood. Methods Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression. Results Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration. Conclusions Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.

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Section: Discussionmentioning

confidence: 99%

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration

Zhang,

Zheng,

Chen

et al. 2024

J Cancer Res Clin Oncol

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“…However, when there is an overexpression of immuneactivating cells and molecules, coupled with a relative insufficiency of immunosuppressive cells and molecules, the body may develop inflammatory and autoimmune diseases, signifying an excess of Yang over Yin [224][225][226]. Conversely, when immunosuppressive cells and molecules surpass immune activation counterparts, the body may be prone to tumor development and immunodeficiency diseases, indicating a dominance of Yin over Yang [227][228][229]. Treating various immune-related diseases by modulating immune cells to restore immunological balance aligns with the principles of traditional Chinese medicine, which aims to harmonize the Yin and Yang forces (Fig.…”

Section: The Chinese "Yin-yang" Theory and Immune Systemmentioning

confidence: 99%

The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology

Cui,

Wang,

et al. 2024

Cell Commun Signal

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The changes in T regulatory cell (Treg) and T helper cell (Th) 17 ratios holds paramount importance in ensuring internal homeostasis and disease progression. Recently, novel subsets of Treg and Th17, namely IL-17-producing Treg and IL-10-producing Th17 have been identified. IL-17-producing Treg and IL-10-producing Th17 are widely considered as the intermediates during Treg/Th17 transformation. These “bi-functional” cells exhibit plasticity and have been demonstrated with important roles in multiple physiological functions and disease processes. Yin and Yang represent opposing aspects of phenomena according to the ancient Chinese philosophy “Yin-Yang” theory. Furthermore, Yin can transform into Yang, and vice versa, under specific conditions. This theory has been widely used to describe the contrasting functions of immune cells and molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) and immune overreaction (inflammation, autoimmunity) can be considered Yang, while immunosuppressive populations (Treg, M2 macrophage, etc.) and immunosuppression (tumor, immunodeficiency) can be considered Yin. However, another important connotation of “Yin-Yang” theory, the conversion between Yin and Yang, has been rarely documented in immune studies. The discovery of IL-17-producing Treg and IL-10-producing Th17 enriches the meaning of “Yin-Yang” theory and further promotes the relationship between ancient “Yin-Yang” theory and modern immunology. Besides, illustrating the functions of IL-17-producing Treg and IL-10-producing Th17 and mechanisms governing their differentiation provides valuable insights into the mechanisms underlying the dynamically changing statement of immune statement in health and diseases.

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NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

Yin,

Song,

et al. 2024

Cancer Immunol Immunother

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The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells’ malignant progression and inhibited T cells’ proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12 −/− ) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-024-03880-6.

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The Yin Yang of Complement and Cancer

Cited by 4 publications

References 105 publications

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration

The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology

NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

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