Expression of NKG2D ligands is downregulated by β-catenin signalling and associates with HCC aggressiveness

Cadoux, Mathilde; Caruso, Stefano; Pham, Sandrine; Gougelet, Angélique; Pophillat, Céline; Riou, Rozenn; Loesch, Robin; Colnot, Sabine; Nguyễn, Công Trung; Caldéraro, Julien; Celton-Morizur, Séverine; Guerra, Nadia; Zucman–Rossi, Jessica; Desdouets, Chantal; Couty, Jean-Pierre

doi:10.1016/j.jhep.2021.01.017

Cited by 46 publications

(43 citation statements)

References 59 publications

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“…This result indicated that ULBP1 could promote the infiltration of NKc into tumors, meaning that HCC with high ULBP1 may possess favorable outcomes. However, a previous study showed that ULBP1 was associated with a poor prognosis in HCC ( 39 ), inconsistent with the above statement. To address this contradiction, we hypothesized that some immune inhibitory factors interact with ULBP1 in HCC.…”

Section: Resultsmentioning

confidence: 81%

“…The mRNA in the network, ULBP1, belongs to the extended MHC class I-like family and acts as one of the major ligands of activatory receptor natural killer cell group 2, member D (NKG2D), which is constitutively expressed on NKc cells, most NKT cells, some gd T cells and CD8 T cells (55). We and others found that ULBP1 is upregulated in HCC tissues and associated with poor prognosis (39). Data from mIF showed that high ULBP1 expression brings out high NKc infiltration in HCC.…”

Section: Discussionmentioning

confidence: 99%

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Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Feng

Zhao

et al. 2021

Front. Oncol.

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Tumor mutation burden (TMB) is associated with immune infiltration, while its underlying mechanism in hepatocellular carcinoma (HCC) remains unclear. A long noncoding RNA (lncRNA)-related competitive endogenous RNA (ceRNA) network can regulate various tumor behaviors, and research about its correlation with TMB and immune infiltration is warranted. Data were downloaded from TCGA and ArrayExpress databases. Cox analysis and machine learning algorithms were employed to establish a lncRNA-based prognostic model for HCC. We then developed a nomogram model to predict overall survival and odds of death for HCC patients. The association of this prognostic model with TMB and immune infiltration was also analyzed. In addition, a ceRNA network was constructed by using DIANA-LncBasev2 and the starBase database and verified by luciferase reporter and colocalization analysis. Multiplex immunofluorescence was applied to determine the correlation between ULBP1 and PD-L1. An eight-lncRNA (SLC25A30-AS1, HPN-AS1, LINC00607, USP2-AS1, HCG20, LINC00638, MKLN1-AS and LINC00652) prognostic score model was constructed for HCC, which was highly associated with TMB and immune infiltration. Next, we constructed a ceRNA network, LINC00638/miR-4732-3p/ULBP1, that may be responsible for NK cell infiltration in HCC with high TMB. However, patients with high ULBP1 possessed a poorer prognosis. Using multiplex immunofluorescence, we found a significant correlation between ULBP1 and PD-L1 in HCC, and patients with high ULBP1 and PD-L1 had the worst prognosis. In brief, the eight-lncRNA model is a reliable tool to predict the prognosis of HCC patients. The LINC00638/miR-4732-3p/ULBP1 axis may regulate immune escape via PD-L1 in HCC with high TMB.

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Section: Resultsmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Feng

Zhao

et al. 2021

Front. Oncol.

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“…The former subset is a mature cytotoxic group that accounts for the majority of circulating NK cells, while the latter subset is less mature, less cytotoxic, primarily immunomodulatory, and mostly be found in secondary lymphoid organs (38). It was well demonstrated that NK cells function in tumor immunosurveillance as they can kill cancer cells without prior sensitization (39)(40)(41). As a kind of important tumor-infiltrating lymphocytes (TILs), low-expressed NK cells are discovered on multiple cancers, which are linked with a poor prognosis of patients, too (42,43).…”

Section: Discussionmentioning

confidence: 99%

Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

Zhang¹,

He²,

Cai³

et al. 2021

Front. Oncol.

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BackgroundLung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.MethodsWe analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.ResultsIL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.ConclusionThe IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.

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“…NK group 2 member (NKG2D) is expressed in NK cells, CD8 + T cells, and γδ T cell active receptors, which recognize the corresponding ligands, such as major histocompatibility complex class I chain-related molecule A or B (MICA/B) and UL16-binding protein (ULBP) ( Perez et al, 2019 ; Cadoux et al, 2021 ). Tumor cells can escape NKG2D- mediated immune monitoring by downregulating the expression of NKG2D ligands on the cell surface.…”

Section: Anticancer Gold Compounds and The Immune Systemmentioning

confidence: 99%

Gold Compounds and the Anticancer Immune Response

Zhou

Liu

et al. 2021

Front. Pharmacol.

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Gold compounds are not only well-explored for cytotoxic effects on tumors, but are also known to interact with the cancer immune system. The immune system deploys innate and adaptive mechanisms to protect against pathogens and prevent malignant transformation. The combined action of gold compounds with the activated immune system has shown promising results in cancer therapy through in vivo and in vitro experiments. Gold compounds are known to induce innate immune responses; however, these responses may contribute to adaptive immune responses. Gold compounds play the role of a major hapten that acts synergistically in innate immunity. Gold compounds support cancer cell antigenicity and promote anti-tumor immune response by inducing the release of CRT, ATP, HMGB1, HSP, and NKG2D to enhance immunogenicity. Gold compounds affect various immune cells (including suppressor regulatory T cells), inhibit myeloid derived suppressor cells, and enhance the function and number of dendritic cells. Gold nanoparticles (AuNPs) have potential for improving the effect of immunotherapy and reducing the toxicity and side effects of the treatment process. Thus, AuNPs provide an ideal opportunity for exploring the combination of anticancer gold compounds and immunotherapeutic interventions.

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Expression of NKG2D ligands is downregulated by β-catenin signalling and associates with HCC aggressiveness

Cited by 46 publications

References 59 publications

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

Gold Compounds and the Anticancer Immune Response

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