Abstract
Colorectal cancer (CRC) remains a devastating human malignancy with poor prognosis. Of the various factors, immune evasion mechanisms play pivotal roles in CRC progression and impede the effects of cancer therapy. Myeloid-derived suppressor cells (MDSCs) constitute an immature population of myeloid cells that are typical during tumor progression. These cells have the ability to induce strong immunosuppressive effects within the tumor microenvironment (TME) and promote CRC development. Indeed, MDSCs have been shown to accumulate in both tumor-bearing mice and CRC patients, and may therefore become an obstacle for cancer immunotherapy. Consequently, numerous studies have focused on the characterization of MDSCs and their immunosuppressive capacity, as well as developing novel approaches to suppress MDSCs function with different approaches. Current therapeutic strategies that target MDSCs in CRC include inhibition of their recruitment and alteration of their function, alone or in combination with other therapies including chemotherapy, radiotherapy and immunotherapy. Herein, we summarize the recent roles and mechanisms of MDSCs in CRC progression. In addition, a brief review of MDSC-targeting approaches for potential CRC therapy is presented.
Highlights
Colorectal cancer (CRC) remains the third most common cancer and the third leading cause of cancer-related deaths in males and females [1]
Human fibrocytic Myeloid-derived suppressor cells (MDSCs) (F-MDSCs), which can be differentiated from umbilical cord blood (UCB) precursors, have been identified as a new MDSCs subset with fibrocytic phenotypes and immunosuppressive functions
This leads to nitration of the T cell receptor-alpha-beta (TCRab) chain, resulting in T cells that lack the ability to interact with the peptide antigen bound to the major histocompatibility complex class II (MHC-II) and are unable to initiate an anti-cancer response [51]
Summary
Colorectal cancer (CRC) remains the third most common cancer and the third leading cause of cancer-related deaths in males and females [1]. Despite improvements in systemic treatments for advanced CRC in recent years, only 12–14% of patients with metastatic CRC survive for five years [2]. Patients with advanced CRC develop resistance to chemotherapy, radiotherapy, immunotherapy and targeted drug therapy, which results in increasing challenges in treating CRC. Different types of immune cells such as myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), tumor-associated macrophages (TAMs), natural killer (NK) cells, and regulatory T cells (Tregs) were shown to impact CRC progression [3, 4]
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