Low Intratumoral CD200 Protein Expression in Primary Merkel Cell Carcinoma Is a Strong Predictor for Disease RelapseGambichler, Girke, Abu Rached
et alCancers (Basel) (2025) 17 (5)
Abstract: Merkel cell carcinoma (MCC) is a rare and frequently fatal form of skin cancer. Apart from Programmed Cell Death Protein 1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) signaling, there is a lack of knowledge regarding other immune checkpoint molecules. Recent studies have observed elevated glycoprotein CD200 (also known as OX-2) mRNA expression in in different types of tumors, with CD200R-expressing myeloid cells present in the tumor microenvironment. However, the potential role of the CD200/CD200 axis as an additional checkpoint modulator remains widely unexplored. The aim of this study was to determine the intratumoral protein expression of CD200 as well as CD200R in a larger cohort of MCC patients and to correlate the expression levels with patients' outcomes.In this multicenter study, we investigated 68 patients with MCC (68 primary tumors and 15 corresponding metastases). Immunohistochemistry (IHC) was performed for CD200 as well as CD200R. Digital quantification and analysis of IHC were performed using QuPath-0.2.3.CD200 and CD200R expression was observed in 100% of cases. Univariate analysis revealed that low CD200 expression in primary tumors (p = 0.0007, HR 9.35), male sex (p = 0.045, HR 2.41), and immunosuppression (p = 0.0031, HR 6.36) were significantly associated with MCC relapse. Low CD200 expression was also linked to prior immune checkpoint inhibitors (ICI) and/or chemotherapy treatment (p = 0.037). Multivariable analysis confirmed that low CD200 expression (p = 0.0012, HR 5.25) and immunosuppression (p = 0.0056, HR 4.11) were independent predictors of MCC relapse.Expression of CD200/CD200R proteins is very high in MCC and may thus be of diagnostic value. More importantly, low intratumoral CD200 protein expression in primary MCC represents a robust independent predictor of MCC relapse.
Human pluripotent stem cell-derived hepatic progenitors exhibit a partially hypoimmunogenic phenotype and actively inhibit immune responsesGantier, Ménoret, Fourrier
et alFront Immunol (2025) 16, 1507317
Abstract: GStemHep cells are human cryopreserved hepatic progenitors derived from pluripotent of stem cells (GStem cells) using a cGMP-compliant protocol. They were highly effective in rescuing mice from acute liver failure.The objective of this study was to analyze the immunogenicity and immunoregulatory properties of GStemHep cells.As compared to GStem cells, GStemHep cells showed complete loss of HLA-I (ABC) and they lacked of expression of HLA-II, HLA-G, HLA-E and PD-L1. GStemHep cells also showed increased expression of CD47, maintained high expression of indoleamine 2,3-dioxygenase (IDO) and heme oxygenase-1 (HO-1) and reduced expression of CD200. In comparison with GStem cells, GStemHep cultured in inflammatory conditions increased the expression of PD-L1, CD200, HO-1, HLA-E, CD47 and HLA-I (ABC) as well as maintained expression of IDO and were negative for HLA-II and HLA-G. GStemHep culture in basal or inflammatory conditions has a low or absent immunogenic activity on T cells, associated to a suppressive effect on proliferation partially mediated by IDO. We observed phagocytosis of GStemHep by macrophages that was partially inhibited by CD47 expression. NK cells were activated by resting GStemHep cells. Upon culture in inflammatory conditions that induced expression of HLA-I molecules in GStemHep cells NK cell activation was reduced. Thus, GStemHep cells are partially hypoimmune cells due to the expression of several immune checkpoint inhibitors and the absence of HLA-I molecules. In inflammatory conditions, the expression of several of these molecules was increased but also of HLA-I that could be immunogenic for T cells but it was inhibitory for NK cells.GStemHep cells show a favorable immunological profile for their use as allogeneic off-the shelf treatment of liver diseases with loss of hepatocyte function.Copyright © 2025 Gantier, Ménoret, Fourrier, Delbos, Nguyen and Anegon.
Monocytes from patients with myelodysplastic syndrome inhibit natural killer cell-mediated antitumor function through the CD200/CD200R pathwayGuo, Liu, Tian
et alInt Immunopharmacol (2025) 152, 114394
Abstract: Reports on the expression of CD200 in monocytes are scarce, and the role of monocytes in patients with myelodysplastic syndrome (MDS) remains unclear. Additionally, monocytes have been implicated in suppressing NK cell function. Therefore, this study aimed to explore the possible mechanism by which monocytes regulate NK cell function through CD200 in patients with MDS.We collected samples from patients with MDS, those with acute myeloid leukemia, and healthy controls. We detected the expression of CD200 on the surface of monocytes and its receptor CD200R on the surface of NK cells using flow cytometry, explored the effect of the CD200/CD200R pathway on activating STAT3 and ERK of NK cells, and studied the effect of blocking CD200/CD200R pathway on NK cells.The expression of CD200 on the surface of monocytes and CD200R on the surface of NK cells in patients with MDS was higher than those in healthy controls. After adding CD200 monoclonal antibody to the co-culture system of monocytes and NK cells, the expression of activated receptors CD107a, CD226, and NKG2D on NK cells significantly increased. We then used siRNA to silence CD200R expression in NK-92 cells and found that the blockade of CD200R enhanced the phosphorylation levels of ERK and STAT3.Our study found that elevated CD200 expression on monocytes in patients with MDS correlates with poor prognosis, suggesting CD200 as a potential prognostic marker. Blocking CD200 enhances NK cell activation and cytotoxicity, indicating that CD200 blockade therapy could enhance antitumor responses in patients with MDS.Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Influence of synthesis temperature on the active performance of doped‑carbon dots embedded in polyvinyl alcohol and their potential for active food packagingThanawutthiphong, Kaewpetch, Wanmolee
et alFood Res Int (2025) 205, 115999
Abstract: This study explores how synthesis temperature influences the properties and functionalities of sulfur‑nitrogen doped carbon dots (S,N-doped CDs) derived from citric acid and cysteine. The focus lies on their potential in bionanocomposite films for active packaging. Bionanocomposite films were prepared by incorporating CDs synthesized at different temperatures (160, 180, and 200 °C) into a polyvinyl alcohol (PVOH) matrix. CD160 displayed a crystalline structure below 10 nm and demonstrated the strongest antifungal and antibacterial activity, as evidenced by the largest clear zones. This superior performance is presumably due to their high N and S content, as shown by the larger redshift in their photoluminescence spectra upon longer wavelength excitation and elemental analysis. CD180 lacked well-defined lattice fringes, indicating an amorphous structure with larger cluster sizes ranging from 10 to 100 nm. Interestingly, UV-blocking and antibacterial efficacy of both films remained high (over 95% UVA block and 5 log10 CFU/mL reduction in bacteria) regardless of CD crystallinity and size. However, the PVOH-CD180 film exhibited more photoluminescence, most likely due to larger defect-related emission centers. In contrast, CD200 had the weakest antifungal and antibacterial activity. While the PVOH-CD200 film achieved a 5 log10 CFU/mL reduction in Gram-positive bacteria, it only managed a 4 log10 CFU/mL reduction in Gram-negative bacteria under contact conditions at 37 °C for 24 h. In addition, the PVOH-CD200 film had the highest antioxidant activity, 88% DPPH radical scavenging, whereas the others had 80%. These findings underscore the critical role of synthesis temperature in tailoring S,N-doped CDs for specific applications within active packaging, where the desired properties dictate the optimal temperature. Preliminary studies suggest that PVOH-CD films have the potential to extend the shelf-life of sweet bread, demonstrating their promise as bionanocomposite active food packaging materials.Copyright © 2025 Elsevier Ltd. All rights reserved.
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