ABSTRACT
Desmoplastic small round-cell tumors (DSRCT) frequently develop in the retroperitoneum, pelvis, omentum, and mesentery. Here, we present an unusual case of primary DSRCT in the liver. The patient was an 11-year-old boy with multiple solid masses in the liver parenchyma. The tumor in the needle biopsy had a histology revealing a small round cell morphology and desmoplasia. It shows the immunohistochemical features of DSRCT and documentation of EWSR1-WT1 fusion.A potential diagnostic pitfall is exerted when evaluating liver biopsy, in which DSRCT is a great mimicker and may be easily confused with more common liver malignancies of childhood, such as hepatoblastoma, calcifying nested stromal-epithelial tumor, undifferentiated embryonal sarcoma, and other small round cell tumors, as well as the fibrolamellar variant of hepatocellular carcinoma. This distinction is critical because an accurate therapeutic approach requires a correct diagnosis.
Subject(s)
Carcinoma, Hepatocellular , Desmoplastic Small Round Cell Tumor , Liver Neoplasms , Sarcoma , Male , Humans , Child , Desmoplastic Small Round Cell Tumor/diagnosis , Desmoplastic Small Round Cell Tumor/genetics , Biopsy , Biopsy, Needle , Liver Neoplasms/diagnosisABSTRACT
In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies.
Subject(s)
Acute Kidney Injury/therapy , Adoptive Transfer , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Lactoferrin/pharmacology , Lung Diseases, Interstitial/therapy , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/transplantation , Pneumonia/therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/immunology , Acute Kidney Injury/metabolism , Animals , Bleomycin , Cell Line, Tumor , Cisplatin , Disease Models, Animal , Drug Therapy, Combination , Female , Humans , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/metabolism , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Ovalbumin , Phenotype , Pneumonia/chemically induced , Pneumonia/immunology , Pneumonia/metabolismABSTRACT
CD45+CD71+ erythroid cells generated through splenic extramedullary erythropoiesis have recently been found to suppress anti-infection and tumor immunity in neonates and adults with malignances. However, their role in tumor microenvironment has not been investigated. In the present study, we found that the number of CD45+CD71+ erythroid cells was significantly elevated in hepatocellular carcinoma (HCC) tissues compared to that in paratumor region and circulation. Additionally, they were more abundant in HCC tissues compared to some immune suppressive cells as well as CD45-CD71+ erythroid cells. CD45+CD71+ erythroid cells suppressed T cells through generation of reactive oxygen species, IL-10, and TGF-ß in a paracrine and cell-cell contact manner, and their suppressive effect was stronger than that of myeloid-derived suppressor cells. The abundance of CD45+CD71+ erythroid cells in tumor tissue, as illustrated via immunofluorescence, predicted disease-free survival and overall survival, and its prognostic value was better than that of Cancer of the Liver Italian Program score. This study demonstrated that accumulation of intratumoral CD45+CD71+ erythroid cells in HCC tissues could play a superior immunosuppressive role in tumor microenvironment and may serve as a valuable biomarker to predict recurrence of HCC.
