Recent insights of the role and signalling pathways of interleukin-34 in liver diseases

Al‐Shaebi, Fadhl; Liang, Wenzhang; Hezam, Kamal; Almezgagi, Maged; Wei, Lin

doi:10.1016/j.intimp.2020.107023

“…Blocking antibodies, particularly PD-1 and CTLA-4, have shifted the paradigm of cancer therapy; however, many patients with cancer do not respond and develop resistance to ICIs. In addition to its vital function in tumors, IL-34 has been identified as a factor that biases macrophages toward immunosuppression, leading to increased tumor evasion and progression ( 28 ). ICIs alone are not sufficient for effective treatment.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer

Al‐Shaebi

¹

,

Safi

²

,

Algabri

³

et al. 2023

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Interleukin-34 (IL-34) is a cytokine that is involved in the regulation of immune cells, including macrophages, in the tumor microenvironment (TME). Macrophages are a type of immune cell that can be found in large numbers within the TME and have been shown to have a role in the suppression of immune responses in cancer. This mmune suppression can contribute to cancer development and tumors’ ability to evade the immune system. Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that target proteins on immune cells that act as “checkpoints,” regulating the activity of the immune system. Examples of these proteins include programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). ICIs work by blocking the activity of these proteins, allowing the immune system to mount a stronger response against cancer cells. The combination of IL-34 inhibition with ICIs has been proposed as a potential treatment option for cancer due to the role of IL-34 in the TME and its potential involvement in resistance to ICIs. Inhibiting the activity of IL-34 or targeting its signaling pathways may help to overcome resistance to ICIs and improve the effectiveness of these therapies. This review summarizes the current state of knowledge concerning the involvement of IL-34-mediated regulation of TME and the promotion of ICI resistance. Besides, this work may shed light on whether targeting IL-34 might be exploited as a potential treatment option for cancer patients in the future. However, further research is needed to fully understand the mechanisms underlying the role of IL-34 in TME and to determine the safety and efficacy of this approach in cancer patients.

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“…Interestingly, the scientific research team of Shanghai Jiao tong University found that increased levels of IL-34 in the acute phase are associated with increased risk of heart failure and poor prognosis after myocardial infarction [22]. IL-34 is also believed to be related to psoriasis, psoriatic arthritis, obesity, liver disease, kidney disease, and inflammatory bowel disease [23][24][25][26][27][28].…”

Section: Bivariate Correlationmentioning

confidence: 99%

Decreased Levels of Serum IL-34 Associated with Cognitive Impairment in Vascular Dementia

Wang

¹

,

Lü

²

,

Ning

³

et al. 2021

BioMed Research International

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Objective. Interleukin- (IL-) 34 is a new type of cytokine with neuroprotective effects discovered in recent years. However, the relationship between IL-34 and vascular dementia (VaD) has not yet been elucidated. The purpose of this study is to determine whether IL-34 is involved in cognitive impairment of VaD. Methods. From January 2017 to December 2020, 84 VaD patients and 60 healthy controls who attended Qingpu Branch of Zhongshan Hospital were prospectively included in the study. Once included in the study, demographic features of all research subjects are collected. They include age, gender, education, white blood cells (WBC), neutrophil, lymphocyte, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Meanwhile, the Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function of participants. The serum IL-34 level was determined by enzyme-linked immunosorbent assay (ELISA). Results. There was no significant difference between the demographic features of VaD patients and healthy controls ( p > 0.05 ). However, the serum IL-34 levels of VaD patients and healthy controls are 27.6 ± 3.9 pg / ml and 41.8 ± 6.0 pg / ml , respectively, and there is a significant statistical difference between them ( p < 0.001 ). The results of bivariate correlation analysis showed that serum IL-34 levels were significantly positively correlated with MoCA scores ( r = 0.371 , p = 0.023 ). Further regression analysis showed that IL-34 was still correlated with MoCA after adjusting for demographic features ( β = 0.276 , p = 0038 ). Conclusions. Serum IL-34 levels in VaD patients were significantly reduced, which may be an independent predictor of cognitive impairment in VaD patients.

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“…High IL-34 expression is associated with poor survival rates and tumor recurrence in patients with HCC. However, the specific mechanisms by which IL-34 influences the occurrence and metastasis of HCC remain unclear 4 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptome sequencing reveals spatial distribution of IL34+ cancer-associated fibroblasts in hepatocellular carcinoma tumor microenvironment

Wang,

Zhou,

Jin

et al. 2023

npj Precis. Onc.

4

0

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We utilized scRNA-seq, a well-established technology, to uncover the gene expression characteristics of IL34+ CAFs within HCC. We analyzed the related mechanisms through in vitro and in vivo assays. To begin, we acquired scRNA-seq datasets about HCC, which enabled us to identify distinct cell subpopulations within HCC tissues. We conducted a differential analysis to pinpoint DEGs associated with normal fibroblasts (NFs) and CAFs. Subsequently, we isolated NFs and CAFs, followed by the sorting of IL34+ CAFs. These IL34+ CAFs were then co-cultured with T cells and HCC cells to investigate their potential role in Tregs infiltration, CD8+ T cell toxicity, and the biological processes of HCC cells. We validated our findings in vivo using a well-established mouse model. Our analysis of HCC tissues revealed the presence of seven primary cell subpopulations, with the most significant disparities observed within fibroblast subpopulations. Notably, high IL34 expression was linked to increased expression of receptor proteins and enhanced proliferative activity within CAFs, with specific expression in CAFs. Furthermore, we identified a substantial positive correlation between IL34 expression and the abundance of Tregs. Both in vitro and in vivo experiments demonstrated that IL34+ CAFs promoted Tregs infiltration while suppressing CD8+ T cell toxicity. Consequently, this promoted the growth and metastasis of HCC. In summary, our study affirms that IL34+ CAFs play a pivotal role in augmenting the proliferative activity of CAFs, facilitating Tregs infiltration, and inhibiting CD8+ T cell toxicity, ultimately fostering the growth and metastasis of HCC.

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Recent insights of the role and signalling pathways of interleukin-34 in liver diseases

Cited by 6 publications

References 58 publications

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer

Decreased Levels of Serum IL-34 Associated with Cognitive Impairment in Vascular Dementia

Single-cell transcriptome sequencing reveals spatial distribution of IL34+ cancer-associated fibroblasts in hepatocellular carcinoma tumor microenvironment

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