Decrease in natural killer cell associated gene expression as a major characteristic of the immune status in the bloodstream of colorectal cancer patients

Xu, Ye; Xu, Qing; Ni, Shu Juan; Liu, Fang; Cai, Guo-Jun; Wu, Fei; Ye, Xun; Xia, Meng; Mougin, Bruno; Cai, San Jun

doi:10.4161/cbt.11.2.13670

Cited by 14 publications

(7 citation statements)

References 12 publications

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“…We identified a list of 1,469 consensus genes that differentially expressed between the controls and CRCs. Our results are consistent with previous studies [3], [5], [9] and show that most DEGs are involved in immune responses, as well as cellular apoptosis, signal transduction, protein transport and gene expression regulation.…”

Section: Discussionsupporting

confidence: 94%

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Gene Expression Analysis of Peripheral Blood Cells Reveals Toll-Like Receptor Pathway Deregulation in Colorectal Cancer

et al. 2013

PLoS ONE

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Colorectal cancer is the leading cause of cancer-related deaths worldwide. The disease is curable when detected at an early stage. However, the compliance rate with current screening recommendations remains poor. An accurate, minimally invasive blood test that has the potential for greater patient compliance would be a welcome addition to the current methods. Recent data have shown that gene expression profile of peripheral blood cells can reflect disease states and thus have diagnostic value. In this study, genome-wide gene expression profiling of peripheral blood cells from 20 healthy controls and 20 colorectal cancer patients were performed using PAXgene™ technology and Affymetrix GeneChip® microarrays. We identified a list of 1,469 genes that were differentially expressed between the healthy controls and cancer patients. Gene annotation and functional enrichment analysis revealed that those genes are mainly related to immune functions. Particularly, a set of genes belonging to the Toll-Like Receptor pathways were up-regulated in the colorectal cancer patients. These findings provide a new understanding of blood gene expression profile in colorectal cancer. Our result may serve as the basis for further development of blood biomarkers for the diagnosis and treatment of colorectal cancer.

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Section: Discussionsupporting

confidence: 94%

“…We and others have previously showed the potential use of gene expression profiling of whole blood samples for cancer detection and diagnosis [3]–[9]. Prior to the clinical manifestation of CRC, which usually takes several years, the host reacts on the implantation of cancer cells via the activated immune system [10].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Analysis of Peripheral Blood Cells Reveals Toll-Like Receptor Pathway Deregulation in Colorectal Cancer

et al. 2013

PLoS ONE

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“…NK cells can affect tumor progression and could represent a surrogate marker of response of the host immunity against cancer cells, including CRC [9]; [10]. NK cell infiltration in situ was found to be minimal within surgically resected CRC samples, as opposed to the higher numbers of NK cells in the adjacent normal mucosa [11].…”

Section: Introductionmentioning

confidence: 98%

Genetic Diversity of the KIR/HLA System and Outcome of Patients with Metastatic Colorectal Cancer Treated with Chemotherapy

Caggiari

Zorzi

et al. 2014

PLoS ONE

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ObjectiveTo explore genes of the killer-cell immunoglobulin-like receptor (KIR) and of the HLA ligand and their relationship with the outcome of metastatic colorectal cancer (mCRC) patients treated with first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI).MethodsA total of 224 mCRC patients were screened for KIR/HLA typing. The determination of the KIR/HLA combinations was based upon the gene content and variants. Genetic associations with complete response (CR), time to progression (TTP) and overall survival (OS) were evaluated by calculating odds and hazard ratios. Multivariate modeling with prognostic covariates was also performed.ResultsFor CR, the presence of KIR2DL5A, 2DS5, 2DS1, 3DS1, and KIR3DS1/HLA-Bw4-I80 was associated with increased CR rates, with median ORs ranging from 2.1 to 4.3, while the absence of KIR2DS4 and 3DL1 was associated with increased CR rates (OR 3.1). After univariate analysis, patients that underwent resective surgery of tumor, absence of KIR2DS5, and presence of KIR3DL1/HLA-Bw4-I80 showed a significant better OS (HR 1.5 to 2.8). Multivariate analysis identified as parameters independently related to OS the type of treatment (surgery; HR 2.0) and KIR3DL1/HLA-Bw4-I80 genotype (HR for T-I80 2.7 and for no functional KIR/HLA interaction 1.8). For TTP, no association with KIR/HLA genes was observed.ConclusionThis study, for the first time, evidences that the genotyping for KIR-HLA pairs are found predictive markers associated with complete response and improves overall survival prediction of FOLFIRI treatment response in metastatic colorectal cancer. These results suggest a role of the KIR/HLA system in patient outcome, and guide new research on the immunogenetics of mCRC through mechanistic studies and clinical validation.

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“…The DCs encompassed clusters of conventional dendritic cells (c19; marked by LY75 ) and plasmacytoid dendritic cells (c18 and c17; marked by CLEC4C ) 22 . The lymphocytes included T cells (c2, c4, and c12; marked by CD3D and CD3G ) 23 , B cells (c16; marked by CD79A and IGHG2 ) 24 , natural killer (NK) cells (c7 and c10; marked by KLRB1 and KLRD1 ) 25 and natural killer T (NKT) cells (c9 and c15; expressing both NK and T cell markers). Detailed analysis revealed that both c2 and c12 belonged to CD4 + helper T cells (marked by CD4 and IL7R ; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing of subcutaneous adipose tissues identifies therapeutic targets for cancer-associated lymphedema

et al. 2022

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Cancer-associated lymphedema frequently occurs following lymph node resection for cancer treatment. However, we still lack effective targeted medical therapies for the treatment or prevention of this complication. An in-depth elucidation of the cellular alterations in subcutaneous adipose tissues of lymphedema is essential for medical development. We performed single-cell RNA sequencing of 70,209 cells of the stromal vascular fraction of adipose tissues from lymphedema patients and healthy donors. Four subpopulations of adipose-derived stromal cells (ASCs) were identified. Among them, the PRG4+/CLEC3B+ ASC subpopulation c3 was significantly expanded in lymphedema and related to adipose tissue fibrosis. Knockdown of CLEC3B in vitro could significantly attenuate the fibrogenesis of ASCs from patients. Adipose tissues of lymphedema displayed a striking depletion of LYVE+ anti-inflammatory macrophages and exhibited a pro-inflammatory microenvironment. Pharmacological blockage of Trem1, an immune receptor predominantly expressed by the pro-inflammatory macrophages, using murine LR12, a dodecapeptide, could significantly alleviate lymphedema in a mouse tail model. Cell–cell communication analysis uncovered a perivascular ligand-receptor interaction module among ASCs, macrophages, and vascular endothelial cells. We provided a comprehensive analysis of the lineage–specific changes in the adipose tissues from lymphedema patients at a single-cell resolution. CLEC3B was found to be a potential target for alleviating adipose tissue fibrosis. Pharmacological blockage of TREM1 using LR12 could serve as a promising medical therapy for treating lymphedema.

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Decrease in natural killer cell associated gene expression as a major characteristic of the immune status in the bloodstream of colorectal cancer patients

Cited by 14 publications

References 12 publications

Gene Expression Analysis of Peripheral Blood Cells Reveals Toll-Like Receptor Pathway Deregulation in Colorectal Cancer

Gene Expression Analysis of Peripheral Blood Cells Reveals Toll-Like Receptor Pathway Deregulation in Colorectal Cancer

Genetic Diversity of the KIR/HLA System and Outcome of Patients with Metastatic Colorectal Cancer Treated with Chemotherapy

Single-cell RNA sequencing of subcutaneous adipose tissues identifies therapeutic targets for cancer-associated lymphedema

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