A Paradoxical Role for Myeloid-Derived Suppressor Cells in Sepsis and Trauma

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells whose numbers dramatically increase in chronic and acute inflammatory diseases, including cancer, autoimmune disease, trauma, burns and sepsis. Studied originally in cancer, these cells are potently immunosuppressive, particularly in their ability to suppress antigen-specific CD8 + and CD4+ T-cell activation through multiple mechanisms, including depletion of extracellular arginine, nitrosylation of regulatory proteins, and secretion of interleukin 10, prostaglandins and other immunosuppressive mediators. However, additional properties of these cells, including increased reactive oxygen species and inflammatory cytokine production, as well as their universal expansion in nearly all inflammatory conditions, suggest that MDSCs may be more of a normal component of the inflammatory response ("emergency myelopoiesis") than simply a pathological response to a growing tumor. Recent evocative data even suggest that the expansion of MDSCs in acute inflammatory processes, such as burns and sepsis, plays a beneficial role in the host by increasing immune surveillance and innate immune responses. Although clinical efforts are currently underway to suppress MDSC numbers and function in cancer to improve antineoplastic responses, such approaches may not be desirable or beneficial in other clinical conditions in which immune surveillance and antimicrobial activities are required.

Tumor- and organ-dependent infiltration by myeloid-derived suppressor cells

“…Our current results demonstrate that tumor infiltration by MDSCs is tumor-dependent and can be associated with a high frequency and absolute number of MDSCs infiltrating into the spleen, liver, lungs, tumor tissue, and PB. It was previously shown that murine MDSCs express low or intermediate levels of CD11c [52] while other studies have suggested higher levels of CD11c expression on MDSCs [25,49,[53][54][55]. In the present study we excluded lymphocytes from analysis (Fig.…”

Acute kidney injury is surprisingly common and a powerful predictor of mortality in surgical sepsis

“…Patients with PICS have a persistent acute phase response (characterized by elevated CRP and undetectable pre-albumin levels) with elevated white blood cell counts but with a very low percentage of lymphocytes[35]. Recent laboratory studies demonstrate the long-term emergence of myeloid derived suppressor cells (MDSCs) during sepsis: immature innate immune cells that suppress lymphocytes but simultaneously cause persistent inflammation.…”

“…Recent laboratory studies demonstrate the long-term emergence of myeloid derived suppressor cells (MDSCs) during sepsis: immature innate immune cells that suppress lymphocytes but simultaneously cause persistent inflammation. We believe they play central role in PICS and this is a current focus of our ongoing research related to MOF pathogenesis[35]. Similarly, emerging evidence suggests that altered homeostasis during AKI leads to an activated innate and adaptive immune response and distant organ dysfunction [22, 36-40].…”

Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines

“…The physiological role of MDSC is thought to lie in the regulation of immune responses to infection and after traumatic stress [3][4][5]. However, increased frequencies of immature myeloid cells with suppressive functions have also been observed in many diVerent types of cancer [6][7][8][9][10][11][12][13][14].…”