Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma

Colorectal carcinoma is one of the most common cancers and is a heterogeneous disease. The inflammatory tumour microenvironment plays a critical role in colorectal carcinoma development. Many researchers have extensively studied tumour-associated macrophages (TAMs), CD8+ cells, IL-17+ cells, TGF...

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Main Author:	Chai, Boon Yean
Format:	Thesis
Language:	English
Published:	2018
Subjects:	Colorectal Neoplasms
Online Access:	http://psasir.upm.edu.my/id/eprint/97910/1/FPSK%28p%29%202021%2011%20-%20IR.1.pdf
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spelling	my-upm-ir.979102022-11-08T02:11:05Z Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma 2018-11 Chai, Boon Yean Colorectal carcinoma is one of the most common cancers and is a heterogeneous disease. The inflammatory tumour microenvironment plays a critical role in colorectal carcinoma development. Many researchers have extensively studied tumour-associated macrophages (TAMs), CD8+ cells, IL-17+ cells, TGF-β and IL-17 expressions as well as Wnt signaling in the tumour microenvironment of colorectal carcinoma. However the relationship between TAMs, CD8+ cells, IL-17+ cells, expression of TGF-β and IL-17 receptors and ligands and Wnt signaling are poorly understood. The main objective of this study is to study interrelationship of M1 TAMs and M2 TAMs with CD8+ cells, IL-17+ cells TGF-βRII, TGF-β, IL-17R, IL-17, and biomolecules of Wnt signaling in the progression of colorectal carcinoma. Double immunohistochemical staining was performed to evaluate densities of CD68+/iNOS M1 TAMs and CD68+/CD163+ M2 TAMs in colorectal carcinoma. Single immunohistochemical staining was performed to determine the density of CD8+ cell and IL-17+ cells and expression of TGF-β and IL-17 receptors and ligands. Using Spearman's correlation, a positive correlation were observed between CD8+ T cells and IL-17+ cells (p=0.031); M1 TAMs and TGF-βRII expression (p<0.001); M1 TAMs and IL-17 expression (p=0.003); IL-17+ cells and IL-17 expression (p=0.031); TGF-βRII expression and IL-17R expression (p=0.011); M2 TAMs and loss of nucleus APC (p=0.013); M2 TAMs and loss of cytoplasmic APC (p=0.011); M1/M2 and loss of cytoplasmic APC (p=0.001); M1 TAMs and p- GSK3β (p=0.003); IL-17+ cells and p-GSK3β (p=0.014); TGF-βRII expression and p-GSK3β (p=0.020). A negative correlation were found between M1 TAMs and CD8+ T cells/IL-17+ cells (p=0.007); M2 TAMs and TGF-β expression (p=0.0007); M2 TAMs and TGF-βRII expression (p=0.049); M1/M2 and TGF-β expression (p=0.031); M1/M2 and TGF-βRII expression (p=0.001). Densities of immune cells and biomolecules in this study were associated with various demographical and clinicopathological features using chi-square test. Early TMN stage was associated with high density of M2 TAMs (p<0.001) and IL- 17+ cells (p<0.001), low CD8+ T cell/IL-17+ cells (p<0.001), high expression of TGF-βRII (p<0.001) and IL-17R (p=0.027). Low histological grade of tumour was associated with high density of IL-17+ cells (p=0.035), high expression of IL-17R (p=0.019) and low CD8+ cell/IL-17+ cells (p=0.030). Decreased depth of tumour invasion (T) was associated with high density of IL-17+ cells (<0.001) and IL-17R (p=0.023). Low lymph nodes metastasis (N) was associated with high density of M2 TAMs (p=0.005) and IL-17+ cells (p<0.001). In conclusion, this study demonstrated that high density of M2 TAMs and IL-17+ cells, high expression of TGF-βRII and IL-17R, and low CD8+ cells/IL-17+ cells are associated with early TNM stage, low histological grade, decreased depth of tumour invasion, low lymph nodes metastasis indicating a favourable prognosis of colorectal carcinoma. M1 TAMs and IL-17 expression are positively correlated TGF-βRII and IL-17+ cells respectively. This implied high density of M1 TAMs and high IL-17 expression also indicating a favourable prognosis. Hence, evaluation of immune cells, ligands and receptors of cytokines may serve as a potential biomarker for assessing colorectal carcinoma progression and developing immune cells/cytokine targeted treatment. Colorectal Neoplasms 2018-11 Thesis http://psasir.upm.edu.my/id/eprint/97910/ http://psasir.upm.edu.my/id/eprint/97910/1/FPSK%28p%29%202021%2011%20-%20IR.1.pdf text en public doctoral Universiti Putra Malaysia Colorectal Neoplasms Seow, Heng Fong
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
advisor	Seow, Heng Fong
topic	Colorectal Neoplasms
spellingShingle	Colorectal Neoplasms Chai, Boon Yean Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma
description	Colorectal carcinoma is one of the most common cancers and is a heterogeneous disease. The inflammatory tumour microenvironment plays a critical role in colorectal carcinoma development. Many researchers have extensively studied tumour-associated macrophages (TAMs), CD8+ cells, IL-17+ cells, TGF-β and IL-17 expressions as well as Wnt signaling in the tumour microenvironment of colorectal carcinoma. However the relationship between TAMs, CD8+ cells, IL-17+ cells, expression of TGF-β and IL-17 receptors and ligands and Wnt signaling are poorly understood. The main objective of this study is to study interrelationship of M1 TAMs and M2 TAMs with CD8+ cells, IL-17+ cells TGF-βRII, TGF-β, IL-17R, IL-17, and biomolecules of Wnt signaling in the progression of colorectal carcinoma. Double immunohistochemical staining was performed to evaluate densities of CD68+/iNOS M1 TAMs and CD68+/CD163+ M2 TAMs in colorectal carcinoma. Single immunohistochemical staining was performed to determine the density of CD8+ cell and IL-17+ cells and expression of TGF-β and IL-17 receptors and ligands. Using Spearman's correlation, a positive correlation were observed between CD8+ T cells and IL-17+ cells (p=0.031); M1 TAMs and TGF-βRII expression (p<0.001); M1 TAMs and IL-17 expression (p=0.003); IL-17+ cells and IL-17 expression (p=0.031); TGF-βRII expression and IL-17R expression (p=0.011); M2 TAMs and loss of nucleus APC (p=0.013); M2 TAMs and loss of cytoplasmic APC (p=0.011); M1/M2 and loss of cytoplasmic APC (p=0.001); M1 TAMs and p- GSK3β (p=0.003); IL-17+ cells and p-GSK3β (p=0.014); TGF-βRII expression and p-GSK3β (p=0.020). A negative correlation were found between M1 TAMs and CD8+ T cells/IL-17+ cells (p=0.007); M2 TAMs and TGF-β expression (p=0.0007); M2 TAMs and TGF-βRII expression (p=0.049); M1/M2 and TGF-β expression (p=0.031); M1/M2 and TGF-βRII expression (p=0.001). Densities of immune cells and biomolecules in this study were associated with various demographical and clinicopathological features using chi-square test. Early TMN stage was associated with high density of M2 TAMs (p<0.001) and IL- 17+ cells (p<0.001), low CD8+ T cell/IL-17+ cells (p<0.001), high expression of TGF-βRII (p<0.001) and IL-17R (p=0.027). Low histological grade of tumour was associated with high density of IL-17+ cells (p=0.035), high expression of IL-17R (p=0.019) and low CD8+ cell/IL-17+ cells (p=0.030). Decreased depth of tumour invasion (T) was associated with high density of IL-17+ cells (<0.001) and IL-17R (p=0.023). Low lymph nodes metastasis (N) was associated with high density of M2 TAMs (p=0.005) and IL-17+ cells (p<0.001). In conclusion, this study demonstrated that high density of M2 TAMs and IL-17+ cells, high expression of TGF-βRII and IL-17R, and low CD8+ cells/IL-17+ cells are associated with early TNM stage, low histological grade, decreased depth of tumour invasion, low lymph nodes metastasis indicating a favourable prognosis of colorectal carcinoma. M1 TAMs and IL-17 expression are positively correlated TGF-βRII and IL-17+ cells respectively. This implied high density of M1 TAMs and high IL-17 expression also indicating a favourable prognosis. Hence, evaluation of immune cells, ligands and receptors of cytokines may serve as a potential biomarker for assessing colorectal carcinoma progression and developing immune cells/cytokine targeted treatment.
format	Thesis
qualification_level	Doctorate
author	Chai, Boon Yean
author_facet	Chai, Boon Yean
author_sort	Chai, Boon Yean
title	Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma
title_short	Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma
title_full	Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma
title_fullStr	Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma
title_full_unstemmed	Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma
title_sort	relationship between tumour-associated macrophages, cd8+ and il17+ cells, tgf-β, tgf-βrii, il-17r and wnt signaling in colorectal carcinoma
granting_institution	Universiti Putra Malaysia
publishDate	2018
url	http://psasir.upm.edu.my/id/eprint/97910/1/FPSK%28p%29%202021%2011%20-%20IR.1.pdf
_version_	1776100277077671936

Relationship between tumour-associated macrophages, CD8+ and IL17+ Cells, TGF-β, TGF-βRII, IL-17R and WNT signaling in colorectal carcinoma

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