Dataset Information

The Immune Cell Landscape in Renal Allografts.

ABSTRACT: Immune cell infiltration plays an important role in the pathophysiology of kidney grafts, but the composition of immune cells is ill-defined. Here, we aimed at evaluating the levels and composition of infiltrating immune cells in kidney grafts. We used CIBERSORT, an established algorithm, to estimate the proportions of 22 immune cell types based on gene expression profiles. We found that non-rejecting kidney grafts were characteristic with high rates of M2 macrophages and resting mast cells. The proportion of M1 macrophages and activated NK cells were increased in antibody-mediated rejection (ABMR). In T cell-mediated rejection (TCMR), a significant increase in CD8 T cell and ??T cell infiltration was observed. CD8 positive T cells were dramatically increased in mixed-ABMR/TCMR. Then, the function of ABMR and TCMR prognostic molecular biomarkers were identified. Finally, we described the gene expression of molecular markers for ABMR diagnosis was elevated and related to the ratio of monocytes and M1 macrophages in ABMR biopsies, while the expression of TCMR diagnosis markers was increased too and positively correlated with ??T cells and activated CD4 memory T cells in TCMR biopsies. Our data suggest that CIBERSORT's deconvolution analysis of gene expression data provides valuable information on the composition of immune cells in renal allografts.

SUBMITTER: Lu J

PROVIDER: S-EPMC7894583 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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The Immune Cell Landscape in Renal Allografts.

Lu Jun J Zhang Yi Y Sun Jingjing J Huang Shulin S Wu Weizhen W Tan Jianming J

Cell transplantation 20210101

Immune cell infiltration plays an important role in the pathophysiology of kidney grafts, but the composition of immune cells is ill-defined. Here, we aimed at evaluating the levels and composition of infiltrating immune cells in kidney grafts. We used CIBERSORT, an established algorithm, to estimate the proportions of 22 immune cell types based on gene expression profiles. We found that non-rejecting kidney grafts were characteristic with high rates of M2 macrophages and resting mast cells. The ...[more]

PMID: 33593079

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Project description:BackgroundADAMTS14 played a crucial role in the formation and development of various cancers. Currently, no associations had been revealed between ADAMTS14 and clear cell renal cell carcinoma (ccRCC). Hence, this study was designed to assess the prognostic values and immunological roles of ADAMTS14 in ccRCC and to reveal its potential mechanisms.MethodsADAMTS14-related expression profiles and related clinical data were downloaded from The Cancer Genome Atlas (TCGA) dataset, validated by the ICGC dataset, qRT-PCR, and immunohistochemistry. We utilized gene set enrichment analysis (GSEA) to find potentially ADAMTS14-related pathways and applied univariate/multivariate Cox regression analyses to identify independent factors significantly related to overall survival (OS) for ccRCC. A nomogram consisted of independent prognostic factors was also conducted. We further explored the associations between ADAMTS14 with immunity and revealed its potential mechanisms.ResultsADAMTS14 displayed a higher expression in ccRCC tumor than in adjacent normal tissues, and further validated results of the ICGC dataset; qRT-PCR and immunohistochemistry remained consistent (all p < 0.05). Moreover, elevated ADAMTS14 expression was significantly associated with poor OS (p < 0.001). Through univariate/multivariate Cox regression analyses, ADAMTS14 was found to be an independent prognostic factor for ccRCC (both p < 0.05) and GSEA identified several signaling pathways including INSULIN, MTOR, and PPAR pathways. The nomogram based on independent prognostic factors was successfully established and well evaluated. Moreover, the expression of ADAMTS14 was remarkably associated with immune checkpoint molecules, tumor mutational burden (TMB), immune cells, and tumor immune microenvironment (all p < 0.05). Results from TIDE and TCIA showed that highly expressed ADAMTS14 could predict worse efficacy of immunotherapy (all p < 0.05). As for its potential mechanisms, we also revealed several LncRNA/RNA binding protein (RBP)/ADAMTS14 mRNA networks.ConclusionsADAMTS14 was found to play oncogenic roles in ccRCC and to be significantly associated with immunity. Several LncRNA/RBP/ADAMTS14 mRNA networks were also identified for its potential mechanisms.

Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage. We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection.

Dataset Information

The Immune Cell Landscape in Renal Allografts.

Publications

The Immune Cell Landscape in Renal Allografts.

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