Mononuclear Phagocyte System Characterisation in Colorectal Cancer and Utility as a Diagnostic Biomarker
Creators: name: Hammer, Clare Paula
Publisher: name: University of Surrey
Year: 2025
Subjects: Mononuclear phagocyte system
CSF1R
Colorectal Cancer

description: lorectal cancer (CRC) is the third most diagnosed cancer and second most deadly in the
description: world. This project deals with characterization of mononuclear phagocyte system (MPS) cells in
description: circulating blood of patients with CRC. This is a pilot study to determine if differences are detected in
description: MPS cells in CRC with the aim of biomarker discovery. There has been an exciting and growing focus
description: in CRC research to identify novel biomarkers and pathogenic mechanisms, especially for detection and
description: treatment of early CRC. CRC incidence has been steadily rising worldwide. There have been great
description: advances in diagnostic and therapeutic methods towards detecting early CRC that is often
description: symptomless. Despite this, CRC is still commonly diagnosed in an advanced stage. Currently a
description: non-specific stool test called Faecal Immunochemical Test (FIT) is used in CRC screening. In addition to FIT
description: being poorly selective, there is also poor patient uptake of this stool based screening test. A blood test
description: that detects CRC is more acceptable for much of the population adding to the rationale for this
description: research focus.
description: Cells from the MPS have emerged as important regulators of cancer development and progression.
description: The MPS comprises monocytes, macrophages, and dendritic cells. Lineage determining cytokines such
description: as colony stimulating factor 1 (CSF1), CSF2 and CSF3 drive the development and differentiation of MPS
description: cells. Blood monocytes are regarded as precursor cells of the MPS; when recruited into the tumour
description: microenvironment they differentiate into tumour-associated macrophages (TAMs). TAMs are a critical
description: component of tumour microenvironment affecting tumour growth, tumour angiogenesis, immune
description: regulation and metastasis. Monocytes represent a window between haematopoiesis in bone marrow
description: and recruitment to tissues as TAMs. I have capitalized on this window to investigate if MPS immune
description: cell changes can be used as proxy of CRC detection and explore cancer therapy targets. Single receptor
description: cytokine inhibition in cancer therapy has not yielded positive results, therefore a greater
description: understanding of what is happening with macrophage receptors in tissues and blood as monocytes is
description: required.
description: I have used fluorescence-activated cell sorting (FACS) with a multicolour panel of antibodies to enable
description: the study of the MPS in blood with new combinations of markers including CSF1R, CSF2R and CSF3R.
description: There are currently no studies measuring expression of CSF1R, 2R or 3R in blood in cancer. In the study
description: of other cancers, higher expression of CSF1R in tumour tissue is associated with worse survival. I have
description: studied CRC tissue with these markers to evaluate if there is correlation between MPS cells in blood
description: and the tumour immune infiltrate in patients with CRC. My results show that CSF1R captures all
description: mononuclear cells subsets described till now. Although evaluating MPS cells based on numbers and
description: expression of CSF1R, CSF2R and CSF3R did not differentiate between CRC and related pathologies,
description: interesting changes in CSF1R positive cells were observed during this study, suggesting
description: reprogramming of these cells during malignancy. In patients with CRC, there is a significant reduction
description: in a subset of dendritic cells with inflammatory function called DC3 (mean DC3 absolute cell count in
description: CRC 3805 cells/mL, control 9564 cells/mL, p=≤0.01 and DC3 mean percentage of total CSF1R cells in
description: CRC 1.15%, control 2.60%, p=≤0.01). DC3 dendritic cells are a recently defined subset and requires
description: ongoing investigation to understand DC3 role in CRC. Studying CRC tissue has shown higher CSF1R
description: expression at the tumour invasive front than the intratumoral region. There also appears that there is
description: a positive correlation with higher CSF1R expression in tissue in the intratumoral region with higher
description: circulating expression of CSF1R.
description: Although this study has not found a clinically relevant biomarker for diagnosing CRC, it has helped in
description: the understanding of the origin and fates of monocytes, and related family members such as dendritic
description: cells. Continued research in this area will establish a clearer picture of all MPS cells in CRC and provide
description: better understanding of the immunopathology leading to CRC