Single‐cell analysis revealed a potential role of T‐cell exhaustion in colorectal cancer with liver metastasis DOI Creative Commons

Tianlong Ling,

Cheng Zhang, Ye Liu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8)

Published: April 1, 2024

Abstract Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T‐cell exhaustion on LM in CRC unclear. Single‐cell sequencing data derived from Gene Expression Omnibus database. Data were normalized using Seurat package and subsequently clustered annotated into different cell clusters. The differentiation trajectories epithelial cells T characterized based pseudo‐time analysis. Single‐sample gene set enrichment analysis (ssGSEA) was used calculate scores for clusters identify enriched biological pathways. Finally, communication performed. Nine subpopulations identified samples with LM. proportion increased can be subdivided NK/T cells, regulatory (Treg) exhausted (Tex). In LM, adhesion proliferation activity Tex promoted. Epithelial categorized six subpopulations. transformation primary involved two evolutionary branches cells. at beginning trajectory but end receptor ligands CEACAM5 ADGRE5‐CD55 played critical roles interactions between Treg cell‐epithelial cell, which may promote epithelial‐mesenchymal transition process CRC. are able CRC, turn promotes tumour development. This provides a new perspective treatment diagnosis

Language: Английский

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases DOI Creative Commons
Chong Zhang, Xiangyu Wang, Jie‐Liang Zuo

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(2), P. e006425 - e006425

Published: Feb. 1, 2023

Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated prognostic value and relevant mechanisms TLSs in colorectal cancer liver metastases (CRCLM).603 CRCLM treated by surgical resection from three centers were included. The categorized according their anatomic subregions quantified, a TLS scoring system was established for intratumor region (T score) peritumor (P score). Differences relapse-free survival (RFS) overall (OS) between groups determined. Multiplex immunohistochemical staining (mIHC) used determine cellular composition 40 patients.T score positively correlated superior prognosis, while P negatively associated poor (all p<0.05). Meanwhile, T specific mutation subtype KRAS. Furthermore, enrichment gene expression significantly transcriptomic subtypes CRCLM. Subsequently, mIHC showed that densities Treg cells, M2 macrophages Tfh cells higher than (p=0.029, p=0.047 p=0.041, respectively), frequencies score, scores Next, based on distribution abundance TLSs, an Immune Score combining which into four immune classes different Among them, class more favorable prognoses. C-index Class RFS OS Clinical Risk statistically. These results also confirmed other two validation cohorts.The is patients, novel predicting patients.

Language: Английский

Citations

46
Cross-talk between Myeloid and B Cells Shapes the Distinct Microenvironments of Primary and Secondary Liver Cancer DOI
Zhihang Chen, Guopei Zhang, Xiaoxue Ren

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(21), P. 3544 - 3561

Published: June 23, 2023

The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that are regulator hepatocellular carcinoma (HCC) colorectal cancer metastasis (CRLM) microenvironments. displayed distinct developmental trajectories HCC CRLM. Single-cell analysis revealed IgG+ plasma preferentially accumulated HCC, whereas IgA+ were enriched Mechanistically, recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, CRLM metastatic CCR10-CCL28 signaling. Functionally, promoted protumorigenic formation induced granulocytic myeloid-derived suppressor activation Clinically, increased infiltration was correlated to worse survival, intratumoral neutrophils indicated poor prognosis. Taken together, this study myeloid cell-mediated immunosuppression CRLM, suggesting selectively modulating or tumor-related immunosuppressive regulatory networks might reprogram provide immunotherapeutic strategy for treating cancer.The immunomodulatory patterns tumor-infiltrating cancer, with mediating physiologic processes drive progression.

Language: Английский

Citations

31
Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis DOI Creative Commons
Rui Li, Xuefei Liu, Xudong Huang

et al.

Gut, Journal Year: 2023, Volume and Issue: unknown, P. gutjnl - 330243

Published: Nov. 30, 2023

Objective Metastasis is the major cause of cancer death. However, what types heterogenous cells in primary tumour and how they metastasise to target organs remain largely undiscovered. Design We performed single-cell RNA sequencing spatial transcriptomic analysis colorectal (CRC) metastases liver (lCRC) or ovary (oCRC). also conducted immunofluorescence staining functional experiments examine mechanism. Results Integrative analyses epithelial reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O ( PTPRO ) achaete scute-like 2 ASCL2 expression as metastatic culprit. This comprising distinct subpopulations shows preference. Population 1 (P1) delta-like ligand 4 (DLL4) MAF bZIP transcription factor A (MAFA) are enriched CRC oCRC, thus may be associated ovarian metastasis. P3 having similar pattern cholangiocytes found mainly lCRC, presuming likely culprits that specifically liver. Stem-like interacted cancer-associated fibroblasts endothelial via DLL4-NOTCH signalling pathway from ovary. In oCRC microenvironment, myofibroblasts provide glutamine perform metabolic reprogramming, which essential for localise develop Conclusion uncover mechanism organ-specific

Language: Английский

Citations

23
scRNA-seq of colorectal cancer shows regional immune atlas with the function of CD20+ B cells DOI
Linlin Ji, Gongbo Fu, Mengxi Huang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 584, P. 216664 - 216664

Published: Jan. 21, 2024

Language: Английский

Citations

15
Pathogenetic development, diagnosis and clinical therapeutic approaches for liver metastasis from colorectal cancer (Review) DOI Creative Commons
Zhenhua Jin,

Yin Li,

Yi Hao

et al.

International Journal of Oncology, Journal Year: 2025, Volume and Issue: 66(3)

Published: Feb. 14, 2025

Colorectal cancer (CRC) is a prevalent malignancy and significant proportion of patients with CRC develop liver metastasis (CRLM), which major contributor to CRC‑related mortality. The present review aimed comprehensively examine the pathogenetic development diagnosis CRLM clinical therapeutic approaches for treatment this disease. molecular mechanisms underlying were discussed, including role tumour microenvironment epithelial‑mesenchymal transition. also highlighted importance early detection current challenges in predicting CRLM. Various strategies reviewed, surgical resection, chemotherapy immunotherapy, potential novel therapies, such as selective internal radiation therapy Traditional Chinese Medicine. Despite recent advancements options, remains challenge due complexity heterogeneity CRC. emphasized need multidisciplinary approach integration emerging therapies improve patient outcomes.

Language: Английский

Citations

1
Siglec9 + tumor-associated macrophages predict prognosis and therapeutic vulnerability in patients with colon cancer DOI Creative Commons
Chang Jiang, Qingyang Feng, Yihao Mao

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 130, P. 111771 - 111771

Published: March 1, 2024

Siglec9 has been identified as an immune checkpoint molecule on tumor-associated macrophages (TAMs). Nevertheless, the expression profile and clinical significance of + TAMs in colon cancer (CC) are still not fully understood. Two cohorts from distinct medical centers were retrospectively enrolled. Immunohistochemistry immunofluorescence conducted to evaluate infiltration cells. Single-cell RNA sequencing flow cytometry utilized identify impact tumor environment, which was subsequently validated through bioinformatics analysis TCGA database. Prognosis benefit adjuvant chemotherapy (ACT) also evaluated using Cox regression Kaplan-Meier method. High associated with worse prognosis better 6-month ACT. contributed immunoevasion by promoting immunosuppressive cells dysfunction process CD8 T Additionally, high mesenchymal-featured subtype overexpression VEGF signaling pathway, strongest communication between vascular endothelial may serve a biomarker for response ACT CC. Furthermore, immunoevasive contexture angiogenesis stimulated suggest potential treatment combinations CC patients.

Language: Английский

Citations

8
Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer DOI
Sheng Yang, Dongsheng Zhang, Qingyang Sun

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(13), P. 2202 - 2217

Published: April 24, 2024

Colorectal cancer is one of the most common malignant tumors in humans, with liver metastasis being primary cause mortality. The epithelial-mesenchymal transition (EMT) process endows cells enhanced metastatic potential. To elucidate cellular mechanisms driving EMT colorectal cancer, we analyzed single-cell RNA sequencing data from 11 nonmetastatic (TnM) and (TM) patients. Compared TnM group, TM samples showed elevated numbers epithelial cell cancer-associated fibroblast (CAF) subsets that displayed enrichments EMT, angiogenesis, TGFβ signaling pathways. One specific TM-enriched subgroup underwent to transdifferentiate into CXCL1+ CAFs subsequently differentiated SFRP2+ CAFs, which was validated by spatial transcriptomic pseudotime trajectory analyses. Furthermore, cell-cell communication analysis identified BHLHE40 as a probable key transcription factor associated poor prognosis. Finally, vitro vivo experiments functionally substantiated promoted proliferation, invasion, migration, cells. In summary, this study regulating promotes cancer. Significance: Integrated transcriptomics provides insights underlying differentiation, could help improve patient diagnosis treatment.

Language: Английский

Citations

8
Crosstalk between gut microbiota and metastasis in colorectal cancer: implication of neutrophil extracellular traps DOI Creative Commons
Jiawei Wu,

Wenyan Dong,

Yayun Pan

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 23, 2023

Primary colorectal cancer (CRC) often leads to liver metastasis, possibly due the formation of pre-metastatic niche (PMN) in liver. Thus, unravelling key modulator metastasis is important for development clinical therapies. Gut microbiota dysregulation a event during CRC progression and metastasis. Numerous studies have elucidated correlation between specific gut bacteria strains (e.g., pks + E. coli Bacteroides fragilis ) initiation, translocation commonly witnessed progression. shapes tumor microenvironment (TME) through direct contact with immune cells or its functional metabolites. However, how facilitates remains controversial. Meanwhile, recent identify dissemination from lumen liver, suggesting role shaping PMN. A pro-tumoral PMN characterized by infiltration immunosuppressive increased pro-inflammatory responses. Notably, neutrophils form web-like structures known as neutrophil extracellular traps (NETs) both primary TME metastatic sites, NETs are involved In this review, we focus on highlight multiple functions different cell types TME, especially NETs, discuss possible mechanisms formation, provide therapeutical indications clinic.

Language: Английский

Citations

14
Immunomodulatory Molecules in Colorectal Cancer Liver Metastasis DOI

W. Kong,

Jia-Jun Li,

Yuqing Deng

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217113 - 217113

Published: July 14, 2024

Language: Английский

Citations

5
B cells in tumor metastasis: friend or foe? DOI Creative Commons

Yuqiu Xu,

Yihao Mao, Yang Lv

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(8), P. 2382 - 2393

Published: Jan. 1, 2023

Metastasis is an important cause of cancer-related death.Immunotherapy may be effective way to prevent and treat tumor metastasis in the future.Currently, many studies have focused on T cells, whereas fewer B cells their subsets.B play role metastasis.They not only secrete antibodies various cytokines but also function antigen presentation directly or indirectly participate immunity.Furthermore, are involved both inhibiting promoting metastasis, which demonstrates complexity immunity.Moreover, different subgroups distinct functions.The functions affected by microenvironment, metabolic homeostasis closely related function.In this review, we summarize analyze mechanisms discuss current status prospects immunotherapy.

Language: Английский

Citations

12