Immunosuppression and Metabolic Changes in Tumor Microenvironment induced by Myeloid-derived Suppressor Cells and its Relationship with Cancer Cachexia

Cancer remain a leading cause of death around the world. Although cancer immunotherapy is widely acknowledged as an important treatment option for cancer, myeloid-derived suppressor cells (MDSCs) have been reported to be a major obstacle to immunotherapy. MDSCs are typically absent or present in very low numbers in healthy individuals; however, they have been reported to markedly increase in pathological conditions including cancer. MDSCs exhibit potent immunosuppressive activity in the tumor microenvironment (TME) through multiple mechanisms, including accumulation of immunosuppressive cells, such as regulatory T cells (Tregs) and tumor associated macrophages (TAMs), as well as the production of reactive oxygen and nitrogen species. Cancer cachexia is characterized by weight loss and hypoalbuminemia, and reported to relate with systemic inflammation that is one of the major inducers of MDSCs. An accumulation of MDSCs is observed in patients with cachexia. Therapeutic modalities targeting MDSCs are under development, with clinical trials currently in progress. Furthermore, in the field of immune-oncology, novel cancer treatments leveraging advanced technologies to target MDSCs have also been reported.