The Role of Myeloid-Derived Suppressor Cells (MDSC) in Cancer Progression

Abstract

The immunosuppressive tumor microenvironment represents not only one of the key factors stimulating tumor progression but also a strong obstacle for efficient tumor immunotherapy. Immunosuppression was found to be associated with chronic inflammatory mediators including cytokines, chemokines and growth factors produced by cancer and stroma cells. Long-term intensive production of these factors induces the formation of myeloid-derived suppressor cells (MDSCs) representing one of the most important players mediating immunosuppression. Moreover, MDSCs could not only inhibit anti-tumor immune reactions but also directly stimulate tumor growth and metastasis. Therefore, understanding the mechanisms of their generation, expansion, recruitment and activation is required for the development of novel strategies for tumor immunotherapy.

Complement in cancer: untangling an intricate relationship

“…Whereas a pioneering study demonstrated that the activation fragment C5a (BOX 1) recruits MDSCs to the tumour microenvironment, resulting in suppressed antitumour immune responses 22 , numerous other investigations have corroborated the view of imbalanced complement activation as a promoter of a pro-inflammatory environment that sustains tumorigenesis. MDSCs, for instance, are increasingly recognized to suppress effector T cells through deprivation of amino acids, production of nitric oxide (NO) and ROS, upregulated expression of programmed cell death 1 ligand 1 (PDL1) and secretion of angiogenic factors 66 . C5a-mediated activation of MDSCs has been associated with the induction of immunomodulators such as arginase 1 (ARG1), cytotoxic T lymphocyte antigen 4 (CTLA4), IL-6, IL-10, lymphocyte activation gene 3 protein (LAG3) and PDL1 in a murine model of lung cancer 67 .…”

Role of liver ICAM-1 in metastasis

“…However, among the immune cell populations recruited from the circulation, MDSCs are able to suppress T cell cytotoxic activity towards the tumor and promote immune suppression (106). In this context, TAMs and MDSCs also contribute to tumor progression by decreasing anti-tumor immunity and generating a pro-tumor microenvironment (106,(121)(122)(123)(124). In fact, macrophages induce apoptosis of peripheral T cells following binding of LFA-1 to ICAM-1 (125), therefore promoting tumor survival through depletion of cytotoxic cells.…”

Gemcitabine nanoparticles promote antitumor immunity against melanoma

“…29,30 LCP-GMP decreased the expressions of immunosuppressive mediators TGF-β, IL-6 and IL-10, suggesting the alleviation of immunosuppression in the TME. IL-6 is important for MDSC generation and survival, 31 and the reduced IL-6 in tumors could promote MDSC depletion. S100 calcium-binding protein A8 (S100A8) and S100A9 are known to induce MDSC expansion and are dependent on STAT3 upregulation.…”