G5 Doctoral dissertation (article)
The roles of immune cell composition and immunosuppressive factors in the colorectal cancer microenvironment (2024)
Immuunisolujen ja immuunivastetta hillitsevien tekijöiden merkitys paksu- ja peräsuolisyövän mikroympäristössä

Elomaa, H. (2024). The roles of immune cell composition and immunosuppressive factors in the colorectal cancer microenvironment [Doctoral dissertation]. University of Jyväskylä. JYU Dissertations, 809. https://urn.fi/URN:ISBN:978-952-86-0244-6

JYU authors or editors

Publication details

All authors or editors: Elomaa, Hanna

eISBN: 978-952-86-0244-6

Journal or series: JYU Dissertations

eISSN: 2489-9003

Publication year: 2024

Number in series: 809

Number of pages in the book: 1 verkkoaineisto (88 sivua, 34 sivua useina numerointijaksoina)

Publisher: University of Jyväskylä

Place of Publication: Jyväskylä

Publication country: Finland

Publication language: English

Persistent website address: https://urn.fi/URN:ISBN:978-952-86-0244-6

Publication open access: Openly available

Publication channel open access: Open Access channel

Abstract

Colorectal cancer is among the most prevalent cancers globally. High immune cell density in the tumor microenvironment has been found to be associated with improved colorectal cancer prognosis. However, the role of certain immune cell types remains incompletely understood. Tumor cells can promote their own growth by suppressing immune cell activity, for example, by upregulating the expression of programmed death-1 (PD-1, PDCD1) and programmed death-ligand 1 (PD-L1, CD274) immune checkpoints, or altering amino acid metabolism through increasing the expression of indoleamine 2,3-dioxygenase (IDO) and arginase-1 (ARG1) enzymes. In this study, immunohistochemistry and machine learning-based image analyses were used to assess the prognostic significance of immune cell densities and distribution, along with the expression of immune suppressive molecules, in colorectal cancer. Multimarker analyses enabled detailed phenotyping of immune cell subtypes and examination of the tumor microenvironment. The overall densities of monocytic cells, granulocytes, or mast cells, or their spatial proximity with tumor cells did not independently associate with colorectal cancer patient survival. However, higher density of T cells, particularly within tumor cell proximity was a strong prognostic indicator of favorable outcome. Moreover, despite the immunosuppressive nature of CD274 and IDO, increased infiltration of CD274+ macrophages and IDO+ monocytic cells was associated with better prognosis in colorectal cancer. These findings enhance the understanding of immune cell infiltration and the spatial interactions between tumor and host immune cells, potentially refining prognostication of colorectal cancer patients and assisting in development of new cancer therapies.

Keywords: cancer of the large intestine; rectal cancer; forecasts; cancer treatments; immune response; immunohistochemistry; cells; dyeing; spatial analysis; machine learning; doctoral dissertations

Free keywords: colorectal carcinoma; immunohistochemistry; inflammatory cell; machine-learning; multimarker staining; prognostic factor; spatial analysis

Contributing organizations

Ministry reporting: Yes

VIRTA submission year: 2024