Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

Sun, Yun‐Fan; Wu, Liang; Zhong, Yu; Zhou, Kaiyu; Hou, Yong; Wang, Zifei; Zhang, Zefan; Xie, Junping; Wang, Chunqing; Chen, Dandan; Huang, Yaling; Wei, Xiaochan; Shi, Ying‐Hong; Zhao, Zhikun; Li, Yuehua; Guo, Ziwei; Yu, Qichao; Xu, Liqin; Volpe, Giacomo; Qiu, Shuang–Jian; Zhou, Jian; Ward, Carl; Sun, Hui‐Chuan; Yin, Ye; Xu, Xun; Wang, Xiangdong; Esteban, Miguel A.; Yang, Huanming; Wang, Jian; Dean, Michael; Zhang, Yaguang; Liu, Shiping; Yang, Xin‐Rong; Fan, Jia

doi:10.1016/j.cell.2020.11.041

Cited by 544 publications

(530 citation statements)

References 93 publications

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“…All these cell subtypes were shared between the two-groups, albeit at different proportions ( Figures 7C , 9A ). The infiltration levels of B cells, tregs were relatively low in all patients, meanwhile the infiltration levels of DCs and the other T cells were higher in all patients ( Figures 7C , 9A ) consistent with a previous report [ 37 ]. Other immune cell types varied between high TMB and low TMB patients, revealing substantial heterogeneity of immune cell compositions among HCC tumors ( Figures 7C , 9A ).…”

Section: Resultssupporting

confidence: 91%

“…Macrophages were significantly enriched in tumors and displayed similar proportions in the immune fractions of high- and low-TMB groups. Although M2 was a dominant Macophages, there were not clearly distinguished in M0, M1 and M2 macrophages, consistent with other previous reports [ 37 , 38 ].…”

Section: Resultssupporting

confidence: 91%

“…Cai et al found that high infiltration of DC in hepatoma indicates a higher disease-free survival time [ 60 ]. Single-cell sequencing of 16,498 HCC cells found that, compared with primary hepatocellular carcinoma, more DCs and CD8+ T cells were infiltrated in early recurrent tumors, while fewer regulatory T cells played an immunosuppressive role [ 37 ] in early recurrent tumors. Due to the high affinity of PD-L1 binding to CD80 on the DC surface, CD80 was preferentially bound to PD-L1.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that the mechanism of immune escape in early recurrent tumors is different from that in primary hepatocellular carcinoma. This will contribute to the development of more effective therapeutic targets and biomarkers for immunotherapy in HCC patients [ 37 ]. According to the origin, DCs are divided into DCs derived from myeloid DC (mDC) and lymphatic dendritic cells (LDC) or plasmacytoid dendritic cells (pDC) [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Prognostic analysis of tumor mutation burden and immune infiltration in hepatocellular carcinoma based on TCGA data

Liu

Tang

Huang

et al. 2021

Aging

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In order to explore the prognosis of tumor mutation burden (TMB) and the relationship with tumor infiltrating immune cells in hepatocellular carcinoma (HCC), we downloaded somatic mutation data and transcriptome profiles of 376 HCC patients from The Cancer Genome Atlas (TCGA) cohort. We divided the samples into high-TMB and low-TMB groups. A higher TMB level indicated improved overall survival (OS) and was associated with early pathological stages. One hundred and nine differentially expressed genes (DEGs) were identified in HCC. Moreover, based on four hub TMB-related signatures, we constructed a TMB Prognostic model (TMBPM) that possessed good predictive value with area under curve (AUC) of 0.701. HCC patients with higher TMBPM scores showed worse OS outcomes (p < 0.0001). Moreover, DCs subsets not only revealed higher infiltrating abundance in the high-TMB group, but also correlated with worse OS and hazard risk for high-TMB patients in HCC. Meanwhile, CD8+ T cells and B cells were associated with improved survival outcomes. In sum, high TMB indicates good prognosis for HCC and promotes HCC immune infiltration. Hence, DCs and the four hub TMB-related signatures can be used for predicting the prognosis in HCC as supplements to TMB.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic analysis of tumor mutation burden and immune infiltration in hepatocellular carcinoma based on TCGA data

Liu

Tang

Huang

et al. 2021

Aging

View full text Add to dashboard Cite

show abstract

“…As a revolutionary technology, single-cell RNA sequencing (single-cell RNA seq) allows for the ability to characterize cell types at the single-cell level and accurately define their various immune functions in the complex tumor microenvironment(TME) (16). Accumulating studies using single-cell RNA seq to explore tumor-infiltrating immune cells have been continuously reported (17–21). Besides, Single-cell RNA seq provides a powerful tool to define the T cell receptor (TCR) sequence and dominant clones recognizing tumor antigens (22).…”

Section: Introductionmentioning

confidence: 99%

Single-cell sequencing characterizes intratumoral profile of immune cells in old mice

Zhang

Lei

Yang

et al. 2021

Preprint

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It has long been thought that aging is a major risk factor for cancer incidence. However, accumulating evidence indicates increased resistance of old animals to tumor growth. A systematic understanding of how old individuals defend against tumor invasion is currently lacking. Here we investigated the differences of age-associated alterations in tumor-infiltrating immune cells between young and old mice using single-cell RNA analysis. Our results showed that a higher proportion of cytotoxic T cells, nTregs, cDC, and M1-type macrophages, while a higher percentage of exhausted T cells, iTregs, pDC, and M2-type macrophages were found in young mice. Importantly, TCR diversity analysis showed top 10 TCR clones consisted primarily of exhausted CD8+ T cells in young mice whereas tip clones were predominantly cytotoxic CD8+ T cells in old mice. Consistently, trajectory inference demonstrated that CD8+ T cells preferentially differentiated into cytotoxic cells in old mice in contrast to exhausted cells in young mice. Meanwhile, we confirmed the main distinctions between young and old mice by flow cytometry. Collectively, our data revealed that a significantly higher proportion of effector immune cells in old mice defend against tumor progression, providing a framework for the immunotherapy of elderly patients with tumors.

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Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment

Moraly,

Kondo,

Benzaoui

et al. 2024

Molecular Oncology

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Tumor‐infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells have demonstrated remarkable success in the treatment of relapsed/refractory melanoma and hematological malignancies, respectively. These treatments have marked a pivotal shift in cancer management. However, as “living drugs,” their effectiveness is dependent on their ability to proliferate and persist in patients. Recent studies indicate that the mechanisms regulating these crucial functions, as well as the T cell's differentiation state, are conditioned by metabolic shifts and the distinct utilization of metabolic pathways. These metabolic shifts, conditioned by nutrient availability as well as cell surface expression of metabolite transporters, are coupled to signaling pathways and the epigenetic landscape of the cell, modulating transcriptional, translational, and post‐translational profiles. In this review, we discuss the processes underlying the metabolic remodeling of activated T cells, the impact of a tumor metabolic environment on T cell function, and potential metabolic‐based strategies to enhance T cell immunotherapy.

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Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

Cited by 544 publications

References 93 publications

Prognostic analysis of tumor mutation burden and immune infiltration in hepatocellular carcinoma based on TCGA data

Prognostic analysis of tumor mutation burden and immune infiltration in hepatocellular carcinoma based on TCGA data

Single-cell sequencing characterizes intratumoral profile of immune cells in old mice

Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment

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