2024

Elomaa, Hanna

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.