Myeloid-derived suppressor cells in colorectal cancer: prognostic biomarkers and therapeutic targets

Abstract

Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells, which are expanded in most cancer patients. MDSCs suppress host immune responses, leading to cancer growth and progression. Several studies demonstrated that there was a relationship between levels of MDSCs and tumorigenesis in colorectal cancer (CRC) patients. MDSCs are now being investigated for their role as possible therapeutic targets in cancer treatment. This review summarizes available studies that investigated MDSC expansion in CRC patients, as well as their role in CRC tumorigenesis, prognosis, and targeting. Based on the available studies, there is a possible relationship between high levels of MDSCs and CRC progression. Additionally, targeting MDSCs in CRC patients selectively represents a significant challenge for the development of targeted treatments. Targeting of MDSCs could be exploited in different ways including MDSC depletion, inhibition of MDSC function and recruitment, and enhancing MDSC differentiation. Overall, MDSCs could be exploited as prognostic biomarkers and potential therapeutic targets in CRC.

Fusobacterium nucleatum in tumors: from tumorigenesis to tumor metastasis and tumor resistance

“… 26 , 27 In the realm of CRC, F. nucleatum exerts its influence by precipitating T cell apoptosis, stifling T cell proliferation, thereby orchestrating a reconfiguration of the tumor microenvironment (TME) conducive to tumorigenesis and metastasis. 74 , 75 Additionally, F. nucleatum interacts with cellular TLR4, instigating the expression of S100A9, a damage-associated molecular pattern protein, and triggering the activation of M2 macrophages through nuclear factor-κB (NF-κB) activation. This cascade, in turn, engenders tumor cell proliferation and migration.…”

Characteristics of the Colorectal Cancer Microenvironment—Role in Cancer Progression and Therapeutic Possibilities

“…In the context of therapy targeted at MDSCs, recent studies by Kang et al report the effective action of metformin, an anti-diabetic drug with anti-tumor properties, which limits undesirable infiltration of MDSCs in CRC [212]. A comprehensive review of the role of MDSCs in colorectal cancer and the targeting of MDSCs in therapy has been conducted by Siemi ńska and Baran, as well as Al-Mterin and Elkord [204,213].…”

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

“…In particular, pCR associated with higher pre-treatment levels of CD8 + T cells, with low expression of PD-1 (PD-1 low CD8 + ), high expression of TRGC2, CD160, KLRB1 and low levels of proliferated and exhausted genes. Myeloid-derived suppressor cells (MDSCs) play a relevant role in the pathogenesis and progression of CRC and are involved in the resistance to immune therapy by suppressing T-cell activity [ 46 , 47 ]. Interestingly, low levels of CD8 + T-cells and high levels of MDSCs in the TME have been recently correlated with resistance to PD-1 inhibitors in dMMR/MSI CRC [ 48 ].…”