IL36 indicating good prognosis in human Hepatocellular Carcinoma

Hu, Miao; Tong, Ying; Fang, Haisheng; Tang, Jie; Hu, Yanni; Li, Jingze; Zhong, Li-Ye

doi:10.7150/jca.47106

Cited by 9 publications

(13 citation statements)

References 27 publications

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“…Our speculation is supported by others, indicating that IL-36 plays a critical role in tumor treatment and prognosis. 29 Furthermore, our data suggest that IL-36α may be a potential therapeutic target in the management of HCC, which is in line with the findings in colorectal cancer during the early stages of the disease. 30 Therefore, we believe that IL-36α is a novel prognostic marker for HCC.…”

Section: Discussionsupporting

confidence: 88%

The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC

Song,

Chu,

Liu

et al. 2023

CMAR

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Purpose To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer. Materials and Methods In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro. Results Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis. Conclusion Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.

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Section: Discussionsupporting

confidence: 88%

The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC

Song,

Chu,

Liu

et al. 2023

CMAR

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“…( Sarin et al, 2020 ) A study results showed that IL-36 was significantly expressed in HCC tumor tissues compared with adjacent peritumoral tissues, and its expression level was closely associated with clinical parameters, such as metastasis, alpha fetoprotein, HBV infection, and cirrhosis, but did not change with age and gender. ( Hu et al, 2020 ) The expression level of IL-36 has also been confirmed to be associated with the prognosis of liver cancer. Specifically, if the expression level of IL-36 was higher, the patients would have a better prognosis of liver cancer and a longer survival time.…”

Section: Introductionmentioning

confidence: 97%

“…These suggested that IL-36 may be a biomarker for HCC. ( Hu et al, 2020 ) Besides, although colorectal cancer (CRC) was the third most common cancer in the world, it was relatively common in Western societies ( Marley and Nan, 2016 ), and the incidence has also increased in China ( Maida et al, 2017 ) IL-36 could be produced at high levels in the colon, which was beneficial to the survival of CRC patients. ( Wang et al, 2014 ) In other words, high IL-36α in CRC patients had higher survival than low IL-36α patients.…”

Section: Introductionmentioning

confidence: 99%

The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

Chen

Yuan

et al. 2021

Front. Pharmacol.

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A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36β, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.

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“…In non-cancerous liver tissues, there is a constitutive level of intrahepatic IL-36; however, the expression of intrahepatic IL-36 is significantly suppressed in HCC tissues (23). Notably, HCC patients with higher intrahepatic IL-36 expression exhibit better survival outcomes, along with lower recurrence rates, compared to HCC patients with lower intrahepatic IL-36 expression (23).…”

Section: Il-36 In Hccmentioning

confidence: 99%

The role of IL-36 and 37 in hepatocellular carcinoma

Cao,

Liu,

Wise

et al. 2024

Front. Immunol.

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Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.

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IL36 indicating good prognosis in human Hepatocellular Carcinoma

Cited by 9 publications

References 27 publications

The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC

The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC

The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

The role of IL-36 and 37 in hepatocellular carcinoma

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