Blocking CD47 promotes antitumour immunity through CD103+ dendritic cell–NK cell axis in murine hepatocellular carcinoma model

Wang, Shuai; Wu, Qinchuan; Chen, Tianchi; Su, Rong; Pan, Caixu; Qian, Junjie; Huang, Hechen; Yin, Shengyong; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

doi:10.1016/j.jhep.2022.03.011

Cited by 88 publications

(48 citation statements)

References 43 publications

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“…2C, the cuproptosis score was lower in malignant cells in ccRCC and higher in tumor and stromal cells at single cell level (Figure S8C, D). Previous studies have indicated that cGAS-STING signaling was correlated with DC in anti-tumor immunity [34][35][36][37][38]. We thus adopted the three ccRCC cohorts to investigate correlation between cuproptosis score and DC signatures, which also showed that cuproptosis score was significantly positive correlated with DC infiltration score (Figure S9A).…”

Section: Cuprotosis In Ccrcc Could Enhance Tumor Immunity Though Cgas...mentioning

confidence: 89%

A new thinking: deciphering the aberrance and clinical implication of copper-death signatures in clear cell renal cell carcinoma

et al. 2022

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Rationale Recent research has indicated that cuprotosis, or copper induced cell death, is a novel type of cell death that could be utilized as a new weapon for cancer management. However, the characteristics and implications of such signatures in cancers, especially in clear cell renal cell cancer (ccRCC), remain elusive. Methods Expression, methylation, mutation, clinical information, copy number variation, functional implication, and drug sensitivity data at the pan-cancer level were collected from The Cancer Genome Atlas. An unsupervised clustering algorithm was applied to decipher ccRCC heterogeneity. Immune microenvironment construction, immune therapy response, metabolic pattern, and cancer progression signature between subgroups were also investigated. Results Cuprotosis related genes were specifically downregulated in various cancer tissues compared with normal tissues and were correlated with hypermethylation and copy number variation. Cuprotosis scores were also dysregulated in tumor tissues, and we found that such a signature could positively regulate oxidative phosphorylation and Myc and negatively regulate epithelial mesenchymal translation and myogenesis pathways. CPCS1 (cuprotosis scores high) and CPCS2 (cuprotosis scores low) in ccRCC displayed distinctive clinical profiles and biological characteristics; the CPCS2 subtype had a higher clinical stage and a worse prognosis and might positively regulate cornification and epidermal cell differentiation to fuel cancer progression. CPCS2 also displayed a higher tumor mutation burden and low tumor stemness index, while it led to a low ICI therapy response and dysfunctional tumor immunity state. The genome-copy numbers of CPCS2, including arm- gain and arm- loss, were higher than those of CPCS1. The prognostic model constructed based on subgroup biomarkers exerted satisfactory performance in both the training and validation cohorts. In addition, overexpression of the copper death activator DLAT suppressed the malignant ability, including cell migration and proliferation, of renal cell lines in vitro and in vivo. Finally, activation of cuprotosis in tumors could enhance antitumor immunity through dsDNA-cGAS-STING signaling in ccRCC. Conclusion The activation of cuprotosis might function as a promising approach among multiple cancers. The cuprotosis related signatures could reshape tumor immunity in the ccRCC microenvironment via cGAS-STING signal, thus activating tumor antigen-presenting process. Upregulation of DLAT expression in ccRCC cell lines could reactivate the copper death pattern and be treated as a suitable target for ccRCC.

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Section: Cuprotosis In Ccrcc Could Enhance Tumor Immunity Though Cgas...mentioning

confidence: 89%

A new thinking: deciphering the aberrance and clinical implication of copper-death signatures in clear cell renal cell carcinoma

et al. 2022

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“…3D-E). These data demonstrated that CD8 T cells from TCF-7 cKO mice may maintain anti-tumor responses by killing the target cells with an NKG2D-mediated mechanism, and by persistent upregulation of Granzyme B expression (Liu et al, 2022;Wang et al, 2022).…”

Section: Loss Of Tcf-7 In Donor Cd8 T Cells Reduced Severity and Pers...mentioning

confidence: 98%

TCF-7is dispensable for anti-tumor response but required for persistent function of mature CD8 T cells

Harris

Mammadli

A³

et al. 2021

Preprint

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for hematological malignancy due to graft-versus-leukemia (GVL) effects, mediated by alloreactive donor T cells. However, these same donor cells cause graft-versus-host disease (GVHD), a life-threatening complication. During GVHD, donor T cells proliferate, migrate, and produce cytokines, leading to damage of healthy host tissues. Separating the linked processes of GVHD and GVL is critical to improving outcomes. Here we show that TCF-1, a major T cell developmental factor, plays a role in regulation of these processes. Using a mouse model of allo-HSCT leading to GVHD, we found that conditional loss of TCF-1 in mature CD8 T cells separates GVHD from GVL, providing an optimal clinical phenotype. This occurred due to changes in cytokine production, proliferation, cell survival, chemokine receptor expression, and gene expression. Thus, modulation of TCF-1 signaling reduces GVHD severity and persistence, but maintains GVL effects, and could be useful for allo-HSCT or other T cell-mediated disorders. Furthermore, here and in our companion manuscript we show that regulation of mature, alloactivated T cells by TCF-1 differs between CD4 and CD8 T cells, suggesting that TCF-1 is critical for regulation of mature alloactivated T cells, with unique programs in each subset.

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“… 30 In HCC, the upregulation of the STING signalling in mregDCs results in CXCL9 and IL‐12 secretion. 31 Di Pilato et al. 32 similarly noted that mregDCs in the perivascular region are also capable of secreting CXCL16 and the cytokine IL‐15.…”

Section: Basic Characteristics Of Mregdcsmentioning

confidence: 99%

Mature dendritic cells enriched in immunoregulatory molecules (mregDCs): A novel population in the tumour microenvironment and immunotherapy target

Zhou

Huang

et al. 2023

Clinical & Translational Med

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Background Dendritic cells (DCs) mediate divergent immune effects by activating T cells or negatively regulating the immune response to promote immune tolerance. They perform specific functions determined by their tissue distribution and maturation state. Traditionally, immature and semimature DCs were described to have immunosuppressive effects, leading to immune tolerance. Nonetheless, recent research has demonstrated that mature DCs can also suppress the immune response under certain circumstances. Main body Mature DCs enriched in immunoregulatory molecules (mregDCs) have emerged as a regulatory module across species and tumour types. Indeed, the distinct roles of mregDCs in tumour immunotherapy have sparked the interest of researchers in the field of single‐cell omics. In particular, these regulatory cells were found to be associated with a positive response to immunotherapy and a favourable prognosis. Conclusion Here, we provide a general overview of the latest and most notable advances and recent findings regarding the basic features and complex roles of mregDCs in nonmalignant diseases and the tumour microenvironment. We also emphasise the important clinical implications of mregDCs in tumours.

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Blocking CD47 promotes antitumour immunity through CD103+ dendritic cell–NK cell axis in murine hepatocellular carcinoma model

Cited by 88 publications

References 43 publications

A new thinking: deciphering the aberrance and clinical implication of copper-death signatures in clear cell renal cell carcinoma

A new thinking: deciphering the aberrance and clinical implication of copper-death signatures in clear cell renal cell carcinoma

TCF-7is dispensable for anti-tumor response but required for persistent function of mature CD8 T cells

Mature dendritic cells enriched in immunoregulatory molecules (mregDCs): A novel population in the tumour microenvironment and immunotherapy target

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