CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes

Colony-stimulating factor 1 receptor (CSF-1R) acts as the receptor for colony stimulating factor 1, a cytokine that controls the production, differentiation, and function of macrophages. Prior studies showed cancer patients harboring germline <i>CSF1R</i> c.1085A>G genetic variant had...

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Autores principales:	Yu-Min Yeh, Peng-Chan Lin, Wu-Chou Su, Meng-Ru Shen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colony-stimulating factor 1 receptor genetic variant CD40 IL-2 expression colorectal cancer Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/228133d9799a4eb980292d600f8a8218
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spelling	oai:doaj.org-article:228133d9799a4eb980292d600f8a82182021-11-25T17:57:55ZCD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes10.3390/ijms2222125651422-00671661-6596https://doaj.org/article/228133d9799a4eb980292d600f8a82182021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12565https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Colony-stimulating factor 1 receptor (CSF-1R) acts as the receptor for colony stimulating factor 1, a cytokine that controls the production, differentiation, and function of macrophages. Prior studies showed cancer patients harboring germline <i>CSF1R</i> c.1085A>G genetic variant had better survival. Here, primary tumor samples from a stage III colorectal cancer (CRC) cohort were analyzed by a targeted gene expression assay containing 395 immune-related genes to study the immune mechanism underlying the different outcomes. CRC patients with <i>CSF1R</i> c.1085 genotype A_G had a better disease-free and overall survival than those with <i>CSF1R</i> genotype A_A. Compared to the group of patients without <i>CSF1R</i> variant, higher <i>CD40LG</i> expression, a surface marker of T cells, was found in the tumor tissues of patients with <i>CSF1R</i> c.1085 variant. In parallel with the higher <i>CD40LG</i> gene expression, immunofluorescent staining also showed more CD3<sup>+</sup>CD40L<sup>+</sup> T cell infiltrates in tumors with <i>CSF1R</i> c.1085 genotype A_G. Moreover, higher IL-2 expression, known to be regulated by CD40 pathway, was also observed in tumors with <i>CSF1R</i> c.1085 genotype A_G than genotype A_A. Higher IL-2 expression generated by the interaction of CD40 ligand and CD40 between T cells and macrophages with <i>CSF1R</i> c.1085A>G variant is the potential mechanism explaining the different outcomes.Yu-Min YehPeng-Chan LinWu-Chou SuMeng-Ru ShenMDPI AGarticlecolony-stimulating factor 1 receptorgenetic variantCD40IL-2 expressioncolorectal cancerBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12565, p 12565 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colony-stimulating factor 1 receptor genetic variant CD40 IL-2 expression colorectal cancer Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	colony-stimulating factor 1 receptor genetic variant CD40 IL-2 expression colorectal cancer Biology (General) QH301-705.5 Chemistry QD1-999 Yu-Min Yeh Peng-Chan Lin Wu-Chou Su Meng-Ru Shen CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
description	Colony-stimulating factor 1 receptor (CSF-1R) acts as the receptor for colony stimulating factor 1, a cytokine that controls the production, differentiation, and function of macrophages. Prior studies showed cancer patients harboring germline <i>CSF1R</i> c.1085A>G genetic variant had better survival. Here, primary tumor samples from a stage III colorectal cancer (CRC) cohort were analyzed by a targeted gene expression assay containing 395 immune-related genes to study the immune mechanism underlying the different outcomes. CRC patients with <i>CSF1R</i> c.1085 genotype A_G had a better disease-free and overall survival than those with <i>CSF1R</i> genotype A_A. Compared to the group of patients without <i>CSF1R</i> variant, higher <i>CD40LG</i> expression, a surface marker of T cells, was found in the tumor tissues of patients with <i>CSF1R</i> c.1085 variant. In parallel with the higher <i>CD40LG</i> gene expression, immunofluorescent staining also showed more CD3<sup>+</sup>CD40L<sup>+</sup> T cell infiltrates in tumors with <i>CSF1R</i> c.1085 genotype A_G. Moreover, higher IL-2 expression, known to be regulated by CD40 pathway, was also observed in tumors with <i>CSF1R</i> c.1085 genotype A_G than genotype A_A. Higher IL-2 expression generated by the interaction of CD40 ligand and CD40 between T cells and macrophages with <i>CSF1R</i> c.1085A>G variant is the potential mechanism explaining the different outcomes.
format	article
author	Yu-Min Yeh Peng-Chan Lin Wu-Chou Su Meng-Ru Shen
author_facet	Yu-Min Yeh Peng-Chan Lin Wu-Chou Su Meng-Ru Shen
author_sort	Yu-Min Yeh
title	CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
title_short	CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
title_full	CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
title_fullStr	CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
title_full_unstemmed	CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes
title_sort	cd40 pathway and il-2 expression mediate the differential outcome of colorectal cancer patients with different <i>csf1r</i> c.1085 genotypes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/228133d9799a4eb980292d600f8a8218
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CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different <i>CSF1R</i> c.1085 Genotypes

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