Immune classification of clear cell renal cell carcinoma

Abstract Since the outcome of treatments, particularly immunotherapeutic interventions, depends on the tumor immune micro-environment (TIM), several experimental and computational tools such as flow cytometry, immunohistochemistry, and digital cytometry have been developed and utilized to classify T...

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Autores principales:	Sumeyye Su, Shaya Akbarinejad, Leili Shahriyari
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f1588e959d940e1b678b1fd5a2615fc
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spelling	oai:doaj.org-article:1f1588e959d940e1b678b1fd5a2615fc2021-12-02T11:02:22ZImmune classification of clear cell renal cell carcinoma10.1038/s41598-021-83767-z2045-2322https://doaj.org/article/1f1588e959d940e1b678b1fd5a2615fc2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83767-zhttps://doaj.org/toc/2045-2322Abstract Since the outcome of treatments, particularly immunotherapeutic interventions, depends on the tumor immune micro-environment (TIM), several experimental and computational tools such as flow cytometry, immunohistochemistry, and digital cytometry have been developed and utilized to classify TIM variations. In this project, we identify immune pattern of clear cell renal cell carcinomas (ccRCC) by estimating the percentage of each immune cell type in 526 renal tumors using the new powerful technique of digital cytometry. The results, which are in agreement with the results of a large-scale mass cytometry analysis, show that the most frequent immune cell types in ccRCC tumors are CD8+ T-cells, macrophages, and CD4+ T-cells. Saliently, unsupervised clustering of ccRCC primary tumors based on their relative number of immune cells indicates the existence of four distinct groups of ccRCC tumors. Tumors in the first group consist of approximately the same numbers of macrophages and CD8+ T-cells and and a slightly smaller number of CD4+ T cells than CD8+ T cells, while tumors in the second group have a significantly high number of macrophages compared to any other immune cell type (P-value $$<0.01$$ < 0.01 ). The third group of ccRCC tumors have a significantly higher number of CD8+ T-cells than any other immune cell type (P-value $$<0.01$$ < 0.01 ), while tumors in the group 4 have approximately the same numbers of macrophages and CD4+ T-cells and a significantly smaller number of CD8+ T-cells than CD4+ T-cells (P-value $$<0.01$$ < 0.01 ). Moreover, there is a high positive correlation between the expression levels of IFNG and PDCD1 and the percentage of CD8+ T-cells, and higher stage and grade of tumors have a substantially higher percentage of CD8+ T-cells. Furthermore, the primary tumors of patients, who are tumor free at the last time of follow up, have a significantly higher percentage of mast cells (P-value $$<0.01$$ < 0.01 ) compared to the patients with tumors for all groups of tumors except group 3.Sumeyye SuShaya AkbarinejadLeili ShahriyariNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sumeyye Su Shaya Akbarinejad Leili Shahriyari Immune classification of clear cell renal cell carcinoma
description	Abstract Since the outcome of treatments, particularly immunotherapeutic interventions, depends on the tumor immune micro-environment (TIM), several experimental and computational tools such as flow cytometry, immunohistochemistry, and digital cytometry have been developed and utilized to classify TIM variations. In this project, we identify immune pattern of clear cell renal cell carcinomas (ccRCC) by estimating the percentage of each immune cell type in 526 renal tumors using the new powerful technique of digital cytometry. The results, which are in agreement with the results of a large-scale mass cytometry analysis, show that the most frequent immune cell types in ccRCC tumors are CD8+ T-cells, macrophages, and CD4+ T-cells. Saliently, unsupervised clustering of ccRCC primary tumors based on their relative number of immune cells indicates the existence of four distinct groups of ccRCC tumors. Tumors in the first group consist of approximately the same numbers of macrophages and CD8+ T-cells and and a slightly smaller number of CD4+ T cells than CD8+ T cells, while tumors in the second group have a significantly high number of macrophages compared to any other immune cell type (P-value $$<0.01$$ < 0.01 ). The third group of ccRCC tumors have a significantly higher number of CD8+ T-cells than any other immune cell type (P-value $$<0.01$$ < 0.01 ), while tumors in the group 4 have approximately the same numbers of macrophages and CD4+ T-cells and a significantly smaller number of CD8+ T-cells than CD4+ T-cells (P-value $$<0.01$$ < 0.01 ). Moreover, there is a high positive correlation between the expression levels of IFNG and PDCD1 and the percentage of CD8+ T-cells, and higher stage and grade of tumors have a substantially higher percentage of CD8+ T-cells. Furthermore, the primary tumors of patients, who are tumor free at the last time of follow up, have a significantly higher percentage of mast cells (P-value $$<0.01$$ < 0.01 ) compared to the patients with tumors for all groups of tumors except group 3.
format	article
author	Sumeyye Su Shaya Akbarinejad Leili Shahriyari
author_facet	Sumeyye Su Shaya Akbarinejad Leili Shahriyari
author_sort	Sumeyye Su
title	Immune classification of clear cell renal cell carcinoma
title_short	Immune classification of clear cell renal cell carcinoma
title_full	Immune classification of clear cell renal cell carcinoma
title_fullStr	Immune classification of clear cell renal cell carcinoma
title_full_unstemmed	Immune classification of clear cell renal cell carcinoma
title_sort	immune classification of clear cell renal cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1f1588e959d940e1b678b1fd5a2615fc
work_keys_str_mv	AT sumeyyesu immuneclassificationofclearcellrenalcellcarcinoma AT shayaakbarinejad immuneclassificationofclearcellrenalcellcarcinoma AT leilishahriyari immuneclassificationofclearcellrenalcellcarcinoma
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Immune classification of clear cell renal cell carcinoma

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