Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer

Theranostics, Год журнала: 2021, Номер 11(7), С. 3089 - 3108

Опубликована: Янв. 1, 2021

Rationale: Siglec15 is an emerging target for normalization cancer immunotherapy. However, pan-cancer anti-Siglec15 treatment not yet validated and the potential role of in bladder (BLCA) remains elusive. Methods: We comprehensively evaluated expression pattern immunological using analysis based on RNA sequencing data obtained from The Cancer Genome Atlas. then systematically correlated with characteristics BLCA tumor microenvironment (TME), including immunomodulators, immunity cycles, tumor-infiltrating immune cells (TIICs), checkpoints, T cell inflamed score. also analyzed predicting molecular subtype response to several options BLCA. Our results were public cohorts as well our microarray cohort, Xiangya cohort. developed risk score (IRS), it, tested its ability predict prognosis Results: found that was specifically overexpressed TME various cancers. hypothesize designs a non-inflamed evidence negatively TIICs, Bladder high sensitive immunotherapy, but exhibited higher incidence hyperprogression. High levels indicated luminal characterized by lower infiltration, immunotherapy neoadjuvant chemotherapy, anti-angiogenic therapy targeted therapies such blocking Siglec15, β-catenin, PPAR-γ, FGFR3 pathways. Notably, combination may be more effective strategy than monotherapy. IRS can accurately Conclusions: Anti-Siglec15 might suitable correlates could options.

Язык: Английский

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METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Фев. 23, 2022

Abstract Background Continual expression of PD-L1 in tumor cells is critical for immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition limited breast cancer. N 6 -methyladenosine (m A) plays a crucial role multiple biological activities. Our study aimed to investigate the regulatory m A modification surveillance Methods MeRIP-seq epitranscriptomic microarray identified that downstream target METTL3. MeRIP-qPCR, absolute quantification assay, RIP-qPCR were used examine molecular mechanism underlying METTL3/m A/IGF2BP3 signaling axis expression. B-NDG BALB/c mice construct xenograft models verify phenotypes upon METTL3 IGF2BP3 silencing. In addition, cancer tissue was analyze correlation between or Results We METTL3-mediated cells. knockdown significantly abolished reduced stabilization mRNA. Additionally, mRNA activation A-IGF2BP3-dependent. Moreover, enhanced anti-tumor immunity PD-L1-mediated activation, infiltration both vitro vivo. also positively correlated with tissues. Conclusion suggested could post-transcriptionally upregulate an A-IGF2BP3-dependent manner further promote mRNA, which may have important implications new efficient therapeutic strategies immunotherapy.

Язык: Английский

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VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy

Journal of Hematology & Oncology, Год журнала: 2020, Номер 13(1)

Опубликована: Июнь 29, 2020

Abstract VISTA (V-domain immunoglobulin suppressor of T cell activation) is a well-established immune regulatory receptor. However, pre-clinical investigations indicated more complicated influences on cancer immunity than previously recognized. Here, we review the current knowledge therapeutic phenotypes and molecular mechanisms that underlie contradictory roles in checking anti-cancer responses. Furthermore, highlight potential indeterminacy VISTA-targeted strategies immunotherapy, with silico analyses. In fact, functions like homeostatic regulator actively normalizes Thus, role remains to be fully elucidated.

Язык: Английский

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Methionine deficiency facilitates antitumour immunity by altering m⁶A methylation of immune checkpoint transcripts

Gut, Год журнала: 2022, Номер 72(3), С. 501 - 511

Опубликована: Июль 8, 2022

Objective Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA antitumour immunity are molecularly intertwined. Design The effect methionine-restricted diet (MRD) feeding was assessed murine models. mechanisms YTH domain-containing family protein 1 (YTHDF1) tumour immune escape were determined vitro vivo. synergistic effects MRD or YTHDF1 depletion with PD-1 blockade also investigated. Results We found that dietary restriction reduced growth enhanced by increasing the number cytotoxicity tumour-infiltrating CD8 + T cells different mouse Mechanistically, S-adenosylmethionine derived from promoted N 6 -methyladenosine (m A) translation checkpoints, PD-L1 V-domain Ig suppressor cell activation (VISTA), cells. Furthermore, m A-specific binding inhibited restoring infiltration cells, synergised for better control. Clinically, expression correlated poor prognosis immunotherapy outcomes cancer patients. Conclusions play critical role anticancer through regulating functions Targeting could be potential new strategy immunotherapy.

Язык: Английский

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CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Март 11, 2021

The chemokine ligand C-X-C motif 11 (CXCL11) is involved in the progression of various cancers, but its biological roles colorectal cancer (CRC) remain confused. Therefore, prognostic value and underlying mechanism CXCL11 CRC were preliminarily evaluated. Three independent datasets used for mRNA-related analysis: one dataset from Cancer Genome Atlas (TCGA, n = 451) two single-cell RNA sequencing (scRNA-seq) Gene Expression Omnibus (GEO): GSE146771 GSE132465. In addition, a colon adenocarcinoma (COAD) patient cohort (the Yijishan Hospital cohort, YJSHC, 108) was utilized analysis cell infiltration by immunohistochemistry. We determined distribution tumor tissue across all TCGA cancers found that expression significantly upregulated both COAD rectal (READ). However, upregulation mRNA associated with better prognosis COAD, not READ. Within patients high abundance intratumoral + cells had prolonged survival ( p 0.001). Furthermore, we group higher proportion antitumor immune cells, lower protumor cells. Additionally, discovered changes gene enriched pathway network mediated CXCL11. Interestingly, cytotoxic genes (IFNG, GZMA, GZMB, GZMK, GZMM, PRF1) immunosuppressive molecules, including PD-L1, positively correlated expression. CXCL11, which promoted immunity to benefit survival, identified as an biomarker COAD.

Язык: Английский

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Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Окт. 13, 2023

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays crucial role in remodeling the tumor microenvironment (TME). Here, through integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups CAFs described their distribution characteristics. Additionally, RNA sequencing (scRNA-seq) from three additional types two newly generated scRNA-seq datasets rare namely epithelial-myoepithelial carcinoma (EMC) mucoepidermoid (MEC), expanded our understanding CAF heterogeneity. Cell-cell interaction conducted within context highlighted pivotal roles matrix (mCAFs) angiogenesis inflammatory (iCAFs) shaping immunosuppressive microenvironment. In patients with breast (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity facilitating proliferation, promoting epithelial-mesenchymal transition (EMT), contributing to establishment an Furthermore, scoring system based on showed significant correlation immune therapy response melanoma patients. Lastly, provided web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for research community investigate pan-cancer.

Язык: Английский

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SERPINE1 Overexpression Promotes Malignant Progression and Poor Prognosis of Gastric Cancer

Journal of Oncology, Год журнала: 2022, Номер 2022, С. 1 - 17

Опубликована: Янв. 29, 2022

The serine protease inhibitor clade E member 1 (SERPINE1) is a major of tissue plasminogen activator and urokinase, has been implicated in the development progression variety tumors. In this study, mRNA microarray TCGA database were used to comprehensively analyze upregulation SERPINE1 gastric cancer (GC) tissues compared with normal stomach tissues. Kaplan-Meier results confirmed that patients high expression exhibited worse overall survival disease-free survival. addition, cell proliferation, scratches, transwell migration invasion assay showed knockdown inhibited GC ells. Western blot VEGF IL-6 was significantly upregulated after overexpression SERPINE1. Meanwhile, positively correlated level immune infiltration using online analysis tools TISIDB TIMER. And increased increase malignancy which detected by Immunohistochemistry. Finally, tumorigenesis experiments nude mice further demonstrated could promote occurrence GC, while deletion GC. summary, highly expressed tissues, helpful for differential diagnosis pathological grade mucosal lesions. might regulate through signaling pathway JAK-STAT3 inflammatory pathway, thus ultimately affecting cells.

Язык: Английский

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MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4814 - 4814

Опубликована: Март 2, 2023

Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in subset of clear cell renal carcinoma (ccRCC). Recent studies suggest that MUC1 plays role modulating metabolism, but its regulating immunoflogosis the tumor microenvironment remains poorly understood. In previous study, we showed pentraxin-3 (PTX3) can affect ccRCC by activating classical pathway complement system (C1q) releasing proangiogenic factors (C3a, C5a). this scenario, evaluated PTX3 expression analyzed potential activation on site immune modulation, stratifying samples tumors high (MUC1H) versus low (MUC1L). We found tissue was significantly higher MUC1H ccRCC. addition, C1q deposition expressions CD59, C3aR, C5aR were extensively present colocalized PTX3. Finally, increased number infiltrating mast cells, M2-macrophage, IDO1+ reduced CD8+ T cells. Taken together, our results modulate infiltrate, promoting immune-silent microenvironment.

Язык: Английский

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Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Март 13, 2023

Abstract Background The incidence and mortality of gastric cancer ranks fifth fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction initiation progression stomach cancer. However, rare prognostic models for mitochondrial-related gene risk been built up in Methods In current study, expression value genes adenocarcinoma (STAD) patients were systematically analyzed to establish a model based on available TCGA GEO databases. tumor microenvironment (TME), immune cell infiltration, mutation burden, drug sensitivity also investigated using R language, GraphPad Prism 8 online Results We established including NOX4, ALDH3A2, FKBP10 MAOA validated its predictive power. This indicated that infiltration high-risk group was significantly different from low-risk group. Besides, score closely related TME signature checkpoint molecules, suggesting immunosuppressive might lead poor prognosis groups. Moreover, TIDE analysis demonstrated combined score, or stromal microsatellite status could more effectively predict benefit immunotherapy STAD with stratifications. Finally, rapamycin, PD-0325901 dasatinib found be effective group, whereas AZD7762, CEP-701 methotrexate predicted Conclusions Our results suggest reliable biomarker personalized treatment patients.

Язык: Английский

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Evodiamine impairs HIF1A histone lactylation to inhibit Sema3A-mediated angiogenesis and PD-L1 by inducing ferroptosis in prostate cancer

European Journal of Pharmacology, Год журнала: 2023, Номер 957, С. 176007 - 176007

Опубликована: Авг. 21, 2023

Язык: Английский

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