Anterior gradient 2–derived peptide upregulates major histocompatibility complex class I–related chains A/B in hepatocellular carcinoma cells

Bian, Jing; He, Linxiu; Wu, Yutong; Liu, Wensi; Ma, Heyao; Sun, Mingli; Yu, Jie-Ping; Yu, Zhaojin

doi:10.1016/j.lfs.2020.117396

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…14 The upregulated expression of MHC class I-related chains A/B induced by AGR2 enhanced the susceptibility of hepatocellular carcinoma to natural killer cells. 31 To summarize, these findings highlight that the Recently published studies indicate that the cellular diversity of tumors is responsible for treatment failure and lethal outcomes in patients with solid tumors. 32 Single-cell transcriptomic data can provide an excellent resolution across cell types.…”

Section: Discussionmentioning

confidence: 84%

Anterior gradient‐2 regulates cell communication by coordinating cytokine–chemokine signaling and immune infiltration in breast cancer

et al. 2023

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Anterior gradient-2 (AGR2) is crucial to breast cancer progression. However, its role in the tumor immune microenvironment remains unclear. RNA sequencing expression profiles and associated clinical information were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. The AGR2 expression patterns were verified using clinical samples of breast cancer. Based on single-cell transcriptomic data, AGR2 expression patterns were identified and cell communication analysis was carried out. Furthermore, the roles of AGR2 in breast tumor progression were explored by a series of functional experiments. We found that DNA methylation was an important mechanism for regulating the expression patterns of AGR2. Patients with AGR2 low expression displayed an immune "hot" and immunosuppressive phenotype characterized by high abundance of tumor immune cell infiltration and increased enrichment scores for transforming growth factorβ (TGFβ) and epithelial-mesenchymal transition pathways, whereas patients with AGR2 high expression showed an opposite immunologic feature with a lack of immune cell infiltration, suggestive of an immune "cold" and desert phenotype. Moreover, single-cell analysis further revealed that AGR2 in malignant cells alters cell-cell interactions by coordinating cytokine-chemokine signaling and immune infiltration. Notably, two immunotherapy cohorts revealed that AGR2-coexpressed genes could serve as prognostic indicators of patient survival. In conclusion, AGR2 could promote breast cancer | 2239 ZHANG et al.

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Section: Discussionmentioning

confidence: 84%

Anterior gradient‐2 regulates cell communication by coordinating cytokine–chemokine signaling and immune infiltration in breast cancer

et al. 2023

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“…Briefly, we collected cell supernatants which cocultured NK cells and A549 and H1299 cells for 4 h. Then, we performed LDH assay. The formula of cytotoxicity was calculated: Cytotoxicity (%) = [(OD Experimental value–OD Spontaneous value)/(OD Maximum value–OD Spontaneous value)] × 100 ( Bian et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity

Song

Jiao

Yan

et al. 2021

Front. Cell Dev. Biol.

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BackgroundLung adenocarcinoma (LUAD) is the most common diagnostic histologic subtype of non-small cell lung cancer, but the role of receptor-type tyrosine-protein phosphatase-like N (PTPRN) in LUAD has not been studied.MethodsWe conducted a bioinformatic analysis to identify the expression of PTPRN on LUAD data from the Cancer Genome Atlas (TCGA) and the relationship between PTPRN and overall survival of LUAD patients. The effects of PTPRN on the migration ability of LUAD cells and the underlying mechanisms were investigated by in vitro and in vivo assays (i.e., wound healing assay, transwell assay, western blotting, xenograft model, and immunohistochemistry). Gene-set enrichment analysis and computational resource were used to analyze the correlation between PTPRN and different tumor-infiltrating immune cells (TIICs). Lactate dehydrogenase assay and Enzyme-linked immunosorbent assay were conducted to examine natural killer (NK) cell cytotoxicity.ResultsIn our study, we found that PTPRN was up-regulated in LUAD and related to metastasis of LUAD patients. Besides, PTPRN was correlated with poor prognosis in the TCGA-LUAD dataset. PTPRN overexpression promoted LUAD cell migration and the expression of EMT markers by influencing MEK/ERK and PI3K/AKT signaling. Moreover, PTPRN expression was significantly associated with TIICs, especially NK cells. A549 and H1299 cells overexpressed PTPRN inhibited NK cell cytotoxicity.ConclusionTaken together, these findings demonstrated that PTPRN might be a potential and novel therapeutic target modulating antitumor immune response in treatment of LUAD.

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“…LA-loaded DCs could not activate NK cells when p38 MAPK of DCs was blocked; thus, activation of p38 MAPK could be the mechanism by which LA upregulated MICA/B expression. Our previous study indicated that peptides could regulate he p38/MAPK pathway to increase MICA/B expression in hepatocellular carcinoma cells [23], whereas the CTL epitope upregulating MICA/B expression on DCs to activate NK cells has not been reported.…”

Section: Discussionmentioning

confidence: 94%

“…showed that the LT peptide could induce antitumour effect of NK cells [23], rather than CTLs. The current study revealed that LA could induce the double-activation of CD8 + T and NK cells, which was not reported in previous researches.…”

Section: Discussionmentioning

confidence: 99%

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8+ T and NK cells: a novel therapeutic tumour vaccine

Liu

et al. 2021

J Hematol Oncol

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Background CD8+ T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8+ T and NK cells. Methods The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Flow cytometry, confocal microscopy, UPLC-QTOF-MS, and RNA-seq were utilized for evaluating immunity of PBMC-derived DCs, CD8+ T or NK cells and related pathways. HLA-A2.1 transgenic mice combined with immunologically reconstituted tumour-bearing mice were used to examine the antitumour effect and safety of epitope vaccines. Results We identified novel HLA-A2.1-restricted extracellular matrix protein 1(ECM1)-derived immunodominant epitopes in which LA induced a potent immune response. We also found that LA-loaded DCs upregulated the frequency of CD3+/CD8+ T cells, CD45RO+/CD69+ activated memory T cells, and CD3−/CD16+/CD56+ NK cells. We demonstrated cytotoxic granule release of LA/DC-CTLs or LA/DC-NK cells and cytotoxicity against tumour cells and microtissue blocks via the predominant IFN-γ/perforin/granzyme B cell death pathway. Further investigating the mechanism of LA-mediated CD8+ T activation, we found that LA could be internalized into DCs through phagocytosis and then formed a LA-MHC-I complex presented onto the DC surface for recognition of the T cell receptor to upregulate Zap70 phosphorylation levels to further activate CD8+ T cells by DC-CTL interactions. In addition, LA-mediated DC-NK crosstalk through stimulation of the TLR4-p38 MAPK pathway increased MICA/B expression on DCs to interact with NKG2D for NK activation. Promisingly, LA could activate CD8+ T cells and NK cells simultaneously via interacting with DCs to suppress tumours in vivo. Moreover, the safety of LA was confirmed. Conclusions LA-induced immune antitumour activity through DC cross-activation with CD8+ T and NK cells, which demonstrated proof-of-concept evidence for the capability and safety of a novel therapeutic tumour vaccine.

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Anterior gradient 2–derived peptide upregulates major histocompatibility complex class I–related chains A/B in hepatocellular carcinoma cells

Cited by 7 publications

References 37 publications

Anterior gradient‐2 regulates cell communication by coordinating cytokine–chemokine signaling and immune infiltration in breast cancer

Anterior gradient‐2 regulates cell communication by coordinating cytokine–chemokine signaling and immune infiltration in breast cancer

Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8+ T and NK cells: a novel therapeutic tumour vaccine

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