Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment

BackgroundImbalanced nutritional supply and demand in the tumor microenvironment often leads to hypoxia. The subtle interaction between hypoxia and immune cell behavior plays an important role in tumor occurrence and development. However, the functional relationship between hypoxia and the tumor mic...

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Main Authors: Luping Zhang, Shaokun Wang, Yachen Wang, Weidan Zhao, Yingli Zhang, Nan Zhang, Hong Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.645320/full
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spelling doaj-4666ff2dd1b4407bb136d1955d98d8122021-03-02T13:50:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.645320645320Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor MicroenvironmentLuping Zhang0Shaokun Wang1Yachen Wang2Weidan Zhao3Yingli Zhang4Nan Zhang5Hong Xu6Department of Gastroenterology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Emergency, The First Hospital of Jilin University, Changchun, ChinaDepartment of Gastroenterology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Gastroenterology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Gastroenterology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Gastroenterology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Gastroenterology, The First Hospital of Jilin University, Changchun, ChinaBackgroundImbalanced nutritional supply and demand in the tumor microenvironment often leads to hypoxia. The subtle interaction between hypoxia and immune cell behavior plays an important role in tumor occurrence and development. However, the functional relationship between hypoxia and the tumor microenvironment remains unclear. Therefore, we aimed to investigate the effect of hypoxia on the intestinal tumor microenvironment.MethodWe extracted the names of hypoxia-related genes from the Gene Set Enrichment Analysis (GSEA) database and screened them for those associated with colorectal cancer prognosis, with the final list including ALDOB, GPC1, ALDOC, and SLC2A3. Using the sum of the expression levels of these four genes, provided by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the expression coefficients, we developed a hypoxia risk score model. Using the median risk score value, we divided the patients in the two databases into high- and low-risk groups. GSEA was used to compare the enrichment differences between the two groups. We used the CIBERSORT computational method to analyze immune cell infiltration. Finally, the correlation between these five genes and hypoxia was analyzed.ResultThe prognosis of the two groups differed significantly, with a higher survival rate in the low-risk group than in the high-risk group. We found that the different risk groups were enriched by immune-related and inflammatory pathways. We identified activated M0 macrophages in TCGA and GEO databases and found that CCL2/4/5, and CSF1 contributed toward the increased infiltration rate of this immune cell type. Finally, we observed a positive correlation between the five candidate genes’ expression and the risk of hypoxia, with significant differences in the level of expression of each of these genes between patient risk groups.ConclusionOverall, our data suggest that hypoxia is associated with the prognosis and rate of immune cell infiltration in patients with colorectal cancer. This finding may improve immunotherapy for colorectal cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2021.645320/fullcolorectal cancerhypoxiaimmune cell infiltrationtumor microenvironmentrisk score
collection DOAJ
language English
format Article
sources DOAJ
author Luping Zhang
Shaokun Wang
Yachen Wang
Weidan Zhao
Yingli Zhang
Nan Zhang
Hong Xu
spellingShingle Luping Zhang
Shaokun Wang
Yachen Wang
Weidan Zhao
Yingli Zhang
Nan Zhang
Hong Xu
Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
Frontiers in Immunology
colorectal cancer
hypoxia
immune cell infiltration
tumor microenvironment
risk score
author_facet Luping Zhang
Shaokun Wang
Yachen Wang
Weidan Zhao
Yingli Zhang
Nan Zhang
Hong Xu
author_sort Luping Zhang
title Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
title_short Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
title_full Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
title_fullStr Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
title_full_unstemmed Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment
title_sort effects of hypoxia in intestinal tumors on immune cell behavior in the tumor microenvironment
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2021-03-01
description BackgroundImbalanced nutritional supply and demand in the tumor microenvironment often leads to hypoxia. The subtle interaction between hypoxia and immune cell behavior plays an important role in tumor occurrence and development. However, the functional relationship between hypoxia and the tumor microenvironment remains unclear. Therefore, we aimed to investigate the effect of hypoxia on the intestinal tumor microenvironment.MethodWe extracted the names of hypoxia-related genes from the Gene Set Enrichment Analysis (GSEA) database and screened them for those associated with colorectal cancer prognosis, with the final list including ALDOB, GPC1, ALDOC, and SLC2A3. Using the sum of the expression levels of these four genes, provided by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the expression coefficients, we developed a hypoxia risk score model. Using the median risk score value, we divided the patients in the two databases into high- and low-risk groups. GSEA was used to compare the enrichment differences between the two groups. We used the CIBERSORT computational method to analyze immune cell infiltration. Finally, the correlation between these five genes and hypoxia was analyzed.ResultThe prognosis of the two groups differed significantly, with a higher survival rate in the low-risk group than in the high-risk group. We found that the different risk groups were enriched by immune-related and inflammatory pathways. We identified activated M0 macrophages in TCGA and GEO databases and found that CCL2/4/5, and CSF1 contributed toward the increased infiltration rate of this immune cell type. Finally, we observed a positive correlation between the five candidate genes’ expression and the risk of hypoxia, with significant differences in the level of expression of each of these genes between patient risk groups.ConclusionOverall, our data suggest that hypoxia is associated with the prognosis and rate of immune cell infiltration in patients with colorectal cancer. This finding may improve immunotherapy for colorectal cancer.
topic colorectal cancer
hypoxia
immune cell infiltration
tumor microenvironment
risk score
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.645320/full
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