Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells that have been implicated in the development of an immunosuppressive environment, which promotes tumorigenesis and tumor progression. Numerous studies have reported expansion of MDSCs in circulation and the tumor microenvironment (TME) of cancer patients. However, due to the heterogenic nature of MDSCs and the different approaches for their identification, their detailed characterization and impact on disease progression in cancer patients are warranted. In this study, we investigated the levels of different myeloid cell subsets and antigen-presenting cells (APCs) using flow cytometry in unfractionated whole blood (WB), peripheral blood mononuclear cells (PBMCs), tumor tissue (TT), and adjacent normal tissue (NT) of colorectal cancer (CRC) patients. We found high levels of granulocytic myeloid cells (GMCs) in whole blood, but their levels were significantly lower in PBMCs. Importantly, we found significantly higher levels of GMCs in the TME compared to NT. In addition, monocytic myeloid cells (MMCs) showed significantly higher levels in PBMCs of CRC patients, compared to healthy donors (HDs). Notably, patients with advanced disease stages showed significantly higher levels of GMCs compared to early stages in whole blood, but PBMCs and tumor-infiltrating myeloid cells did not show any significant differences. Lastly, we found that levels of GMCs decreased, while IMCs increased in the TME with tumor budding. Our results highlight the importance of investigating the levels of different myeloid cell subsets in PBMCs versus whole blood of cancer patients and improve current knowledge on the potential prognostic significance of myeloid cells in CRC patients.

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

“…Studies in CRC patients also show that human MDSCs enhance CRC cell stemness [ 171 ], which accelerates faster cancer cells proliferation. Toor et al showed that levels of tumor-infiltrating MDSC were increased in patients with high tumor budding and advanced stage of CRC suggesting their potential roles in metastasis [ 173 ].…”

Role of T Regulatory Cells and Myeloid-Derived Suppressor Cells in COVID-19

“…Generally, MDSCs in human are defined as CD33 + CD11b + HLA-DR low cells and are classified into two primary subgroups based on differences in cell morphology and cell-surface markers: granulocytic (polymorphonuclear) CD33 + CD11b + HLA-DR low CD15 + cells (G-MDSCs) and monocytic CD33 + CD11b + HLA-DR low CD14 + cells (M-MDSCs) [ 70 – 73 ]. More recently, an additional subgroup has been identified as CD33 + CD11b + HLA-DR low CD14 − CD15 − , and they are named immature or early-stage MDSCs (e-MDSCs) [ 72 , 74 , 75 ].…”

“…MDSC subpopulations of monocytic and granulocytic cells have been identified and characterized in different human cancers [ 82 – 85 ]. They inhibit antitumor immune responses [ 85 – 87 ], and as a result, cancer cells continue to evolve [ 75 ].…”

Intrinsic and acquired cancer immunotherapy resistance

“…Meanwhile, M2 macrophages, polarized by IL-4 and IL-13 favor tumor promotion and create an immuno-subversive environment by interfering with T cell functionality [71]. In addition to these, MDSCs are considered as one of the major immunosuppressive cells, which abundantly exist in the TME [72]. MDSCs are heterogenous population including two major subtypes; polymorphonuclear (PMN-MDSC) or granulocytic (G-MDSCs) and monocytic (M-MDSCs), which have potent immunosuppressive characteristics and favor tumorigenesis and progression [73,74].…”