Single‐cell and spatial transcriptomics reveal POSTN+ cancer‐associated fibroblasts correlated with immune suppression and tumour progression in non‐small cell lung cancer DOI Creative Commons
Chao Chen,

Qiang Guo,

Yang Liu

et al.

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(12)

Published: Dec. 1, 2023

Abstract Background Cancer‐associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, influence CAF subpopulations on progression lung is still unclear, which impedes translational advances in targeting CAFs. Methods We performed single‐cell RNA sequencing (scRNA‐seq) tumour, paired tumour‐adjacent, and normal samples from 16 non‐small cell (NSCLC) patients. were analyzed after integration with published NSCLC scRNA‐seq data. SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) was applied tumour tumour‐adjacent seven patients map architecture major populations microenvironment (TME). Immunohistochemistry (IHC) multiplexed IHC (mIHC) used validate marker gene expression association CAFs immune infiltration TME. Results A subcluster myofibroblastic POSTN + significantly enriched advanced tumours presented signatures related extracellular matrix remodeling, invasion pathways suppression. Stereo‐seq mIHC demonstrated that close localization SPP1 macrophages associated exhausted phenotype lower T cells. or abundance poor prognosis NSCLC. Conclusions Our study identified a subpopulation, might associate promote formation desmoplastic participate Furthermore, we showed clinical outcomes may provide new insights treatment

Language: Английский

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials DOI Creative Commons
Hao Zhang,

Xinghai Yue,

Zhe Chen

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

Citations

146
Precision treatment in advanced hepatocellular carcinoma DOI Creative Commons
Xupeng Yang, Chen Yang, Shu Zhang

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 180 - 197

Published: Feb. 1, 2024

The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, newly developed strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision represents a paradigm shift cancer recent years. This approach utilizes unique molecular characteristics individual patient personalize modalities, aiming maximize efficacy while minimizing side effects. Although precision shown multiple types, its application remains infancy. In this review, we discuss key aspects HCC, including biomarkers, classifications, heterogeneity tumor microenvironment. We also propose future directions, ranging from revolutionizing current methodologies personalizing therapy through functional assays, which will accelerate next phase advancements area.

Language: Английский

Citations

124
Biomarkers for immunotherapy of hepatocellular carcinoma DOI
Tim F. Greten, Augusto Villanueva, Firouzeh Korangy

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(11), P. 780 - 798

Published: Sept. 19, 2023

Language: Английский

Citations

99
Advances in single-cell RNA sequencing and its applications in cancer research DOI Creative Commons
Dezhi Huang,

Naya Ma,

Xinlei Li

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 24, 2023

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition functional capabilities during transition from normal to neoplastic state. Powerful experimental and computational tools can be applied elucidate mechanisms occurrence, progression, metastasis, drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect average gene expression in sample, making it difficult understand tumor heterogeneity microenvironment. The emergence development single-cell (scRNA-seq) technologies have provided opportunities subtle changes biology identifying distinct cell subpopulations, dissecting microenvironment, characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used cancer studies explore which increased understanding tumorigenesis evolution. This review summarizes basic processes their increasing applications research clinical practice.

Language: Английский

Citations

83
Advances in spatial transcriptomics and related data analysis strategies DOI Creative Commons

Jun Du,

Yuchen Yang, Zhijie An

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 18, 2023

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental biological and medical research, have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot spatial information, while allow gene expression to be obtained from intact sections the original physiological context at a resolution. Various insights generated into architecture further elucidation of interaction between cells microenvironment. Thus, we gain general understanding histogenesis processes disease pathogenesis, etc. Furthermore, silico methods involving widely distributed R Python packages for data analysis play essential roles deriving indispensable bioinformation eliminating technological limitations. In this review, summarize available transcriptomics, probe several applications, discuss computational strategies raise future perspectives, highlighting developmental potential.

Language: Английский

Citations

73
The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages DOI Open Access
Eri Matsubara, Hiromu Yano, Cheng Pan

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2250 - 2250

Published: April 12, 2023

Macrophages are a representative cell type in the tumor microenvironment. that infiltrate cancer microenvironment referred to as tumor-associated macrophages (TAMs). TAMs exhibit protumor functions related invasion, metastasis, and immunosuppression, an increased density of is associated with poor clinical course many cancers. Phosphoprotein 1 (SPP1), also known osteopontin, multifunctional secreted phosphorylated glycoprotein. Although SPP1 produced variety organs, at cellular level, it expressed on only few types, such osteoblasts, fibroblasts, macrophages, dendritic cells, lymphoid mononuclear cells. by previous studies have demonstrated correlations between levels circulating and/or expression cells prognosis types cancer. We recently revealed correlated chemoresistance lung adenocarcinoma. In this review, we summarize significance cancers discuss importance new marker for subpopulation monocyte-derived Several shown SPP1/CD44 axis contribute solid cancers, so may represent one most critical mechanisms cell-to-cell communication TAMs.

Language: Английский

Citations

64
Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma DOI
Liren Zhang, Jiali Xu, Suiqing Zhou

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 80(1), P. 82 - 98

Published: Oct. 12, 2023

Language: Английский

Citations

60
Tumor immunotherapy resistance: Revealing the mechanism of PD-1 / PD-L1-mediated tumor immune escape DOI Creative Commons
Jiawen Cui, Yao Li, Yang Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116203 - 116203

Published: Jan. 26, 2024

Tumor immunotherapy, an innovative anti-cancer therapy, has showcased encouraging outcomes across diverse tumor types. Among these, the PD-1/PD-L1 signaling pathway is a well-known immunological checkpoint, which significant in regulation of immune evasion by tumors. Nevertheless, considerable number patients develop resistance to anti-PD-1/PD-L1 rendering it ineffective long run. This research focuses on exploring factors PD-1/PD-L1-mediated immunotherapy. Initially, characterized its role facilitating evasion, emphasizing autoimmune homeostasis. Next, primary mechanisms PD-1/PD-L1-based immunotherapy are analyzed, including antigen deletion, T cell dysfunction, increased immunosuppressive cells, and alterations expression PD-L1 within cells. The possible ramifications altered metabolism, microbiota, DNA methylation also described. Finally, resolution strategies for dealing with discussed, placing particular emphasis personalized therapeutic approaches exploration more potent regimens.

Language: Английский

Citations

41
Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives DOI Creative Commons

Ke-Yu Shen,

Ying Zhu,

Sun‐Zhe Xie

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 29, 2024

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.

Language: Английский

Citations

41
Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma DOI Creative Commons
Nan Zhang, Yang Xu, Mingjian Piao

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 14, 2024

Abstract Systemic therapies using programmed death-1 (PD-1) and death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, prognostic factors, their underlying mechanisms is crucial. In this review, we summarized latest advancements field. Within tumor microenvironment, PD-L1 expression commonly utilized to predict response. Moreover, characteristics of tumor-infiltrating lymphocytes are associated effectiveness immunotherapy. Preclinical studies identified stimulatory dendritic cells, conventional macrophages as potential biomarkers. The emergence single-cell sequencing spatial transcriptomics has provided invaluable insights into heterogeneity through lens profiling distribution. With widespread adoption next-generation sequencing, certain genomic characteristics, including mutational burden, copy number alterations, specific genes (TP53, CTNNB1, GZMB), signaling pathways (WNT/β-catenin) been found correlate prognosis. Furthermore, clinical features such size, number, metastasis status value. Notably, common indicators Child-Pugh score Eastern Cooperative Oncology Group score, which used liver diseases, shown potential. Similarly, employed laboratory parameters baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes alpha-fetoprotein (AFP) abnormal prothrombin, CRAFITY (composed C-reactive protein AFP), immune adverse events predictive Novel imaging techniques EOB-MRI PET/CT employing innovative tracers also liquid biopsy gained use biomarker owing its non-invasive, convenient, highly reproducible nature, well monitoring capabilities. Research on gut microbiome, composition, changes, metabolomic analysis, considerable attention. Efficient discovery relies continuous updating treatment strategies. Next, recent research HCC immunotherapy an overview ongoing trials for contributing understanding improvement

Language: Английский

Citations

34