Immunosuppressive myeloid-derived suppressor cells are increased in splenocytes from cancer patients

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice. We compared the frequency and function of MDSC subsets in dissociated human spleen from 16 patients with benign pancreatic cysts and 26 patients with a variety of cancers. We found that total MDSCs (Linneg CD11bpos CD33pos HLA-DRneg), granulocytic MDSCs (additional markers CD14neg CD15pos), and monocytic MDSCs (CD14pos CD15neg) were identified in human spleen. The monocytic subset was the most prominent in both spleen and peripheral blood and the granulocytic subset was expanded in the spleen relative to matched peripheral blood samples. Importantly, the frequency of CD15pos MDSCs in the spleen was increased in patients with cancer compared to patients with benign pancreatic cysts and was associated with a significantly increased risk of death and decreased overall survival. Finally, MDSCs isolated from the spleen suppressed T cell responses, demonstrating for the first time the functional capacity of human splenic MDSCs. These data suggest that the human spleen is a potential source of large quantities of cells with immunosuppressive function for future characterization and in-depth studies of human MDSCs.

High-Dimensional Analysis of Postsplenectomy Peripheral Immune Cell Changes

“…The macrophages in the red pulp filter blood and recycle iron from erythrocytes. The various immune cells in the white pulp, including B cells, T cells, NK cells, macrophages, and dendritic cells, are able to initiate and regulate innate and acquired immune responses (10,12). It has been speculated that because of the altered hematological and immunological profiles postoperation, asplenic patients have an increased mortality risk regardless of the initial splenectomy indication, compared with the general population (13).…”

Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma

“…The functional significance of this finding is uncertain. Increased splenic granulocytic-MDSCs have been associated with cancer in both humans [32] and mice [33]. This observation may reflect, in part, a consequence of sex hormones regulating differentiation of myeloid cells.…”

Changes of Peripheral Lymphocyte Populations in Patients with Advanced/Recurrent Ovarian Cancer Undergoing Splenectomy During Cytoreductive Surgery

“…The spleen, as the most important peripheral immune organ, plays a negative immunologic role in it [7] .…”

“…As the spleen is one of the most important peripheral immune organs, splenectomy has been suggested to have an impact on immunological function [7] . Some studies found that people with splenectomy have a higher risk of developing overall cancer, as well as certain site-speci c cancers [8,9] .…”