Purpose:To explore whether NDV and/or NDV-induced IFNs regulate programmed death-1 ligand (PD-L1) expression and modulate the balance between inhibitory and stimulatory immune signals. Materials and Methods:Human non-malignant (NB1RGB and HEK293) and tumor (A549 and U87MG) cell lines were used. Cells were either infected with Newcastle disease virus (NDV) LaSota strain or treated with interferons (IFNs). PD-L1 expression was analyzed by flow cytometry, Western blotting, and immunofluorescence. The relationship between PD-L1, as an immune inhibitor, and major histocompatibility complex class I polypeptide-related sequence A (MICA), as an immune activator, was evaluated using duplex chromogenic in situ hybridization. To investigate whether the NDV-induced shift in the PD-L1/MICA axis was sufficient to activate natural killer group 2 member D (NKG2D) receptor-possessing cells within peripheral blood mononuclear cells (PBMCs), IFN-γ production was measured in PBMCs following 24 hours of co-culture with tumor and normal cell lines previously infected with NDV or treated with IFN-λ. Results:NDV infection and IFN treatment resulted in a reduction of PD-L1 expressions in specific cell types. This decrease was accompanied by a concurrent increase in MICA expression, as demonstrated by in situ hybridization. The shift in balance between PD-L1 and MICA correlated with enhanced activation of NKG2D receptor-expressing immune cells, evidenced by increased IFN-γ secretion. Conclusion:These findings suggest that NDV may exert antitumor effects by modulating the balance between inhibitory checkpoint molecules and stimulatory ligands, specifically through downregulation of PD-L1 and upregulation of MICA. This mechanism highlights the potential of NDV to enhance cytotoxic immune responses and supports its further development as a novel strategy in cancer immunotherapy.
Teridah Ernala Ginting,1– 3 Young Othiwi Larasati,1 Vina Cornelia,1 Nur Rahmaniah Hidayat,1 Salomo Christian,1 Kamaluddin Zarkasie,4 Irawan Yusuf1,51Division of Immunology, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Tangerang, Banten, Indonesia; 2Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Banten, Indonesia; 3Global Health Department, Association of Public Health Laboratories, Bethesda, MD, USA; 4Faculty of Veterinary Medicine, PT. IPB Shigeta Animal Pharmaceuticals, Bogor Agricultural University, Bogor, West Java, Indonesia; 5Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, IndonesiaCorrespondence: Teridah Ernala Ginting, Division of Immunology, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Tangerang, Banten, Indonesia; Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Banten, Indonesia, Tel +62 21 5421 0123, Fax +62 21 5421 0110, Email tginting@mrinstitute.orgPurpose: To explore whether NDV and/or NDV-induced IFNs regulate programmed death-1 ligand (PD-L1) expression and modulate the balance between inhibitory and stimulatory immune signals.Materials and Methods: Human non-malignant (NB1RGB and HEK293) and tumor (A549 and U87MG) cell lines were used. Cells were either infected with Newcastle disease virus (NDV) LaSota strain or treated with interferons (IFNs). PD-L1 expression was analyzed by flow cytometry, Western blotting, and immunofluorescence. The relationship between PD-L1, as an immune inhibitor, and major histocompatibility complex class I polypeptide-related sequence A (MICA), as an immune activator, was evaluated using duplex chromogenic in situ hybridization. To investigate whether the NDV-induced shift in the PD-L1/MICA axis was sufficient to activate natural killer group 2 member D (NKG2D) receptor-possessing cells within peripheral blood mononuclear cells (PBMCs), IFN-γ production was measured in PBMCs following 24 hours of co-culture with tumor and normal cell lines previously infected with NDV or treated with IFN-λ.Results: NDV infection and IFN treatment resulted in a reduction of PD-L1 expressions in specific cell types. This decrease was accompanied by a concurrent increase in MICA expression, as demonstrated by in situ hybridization. The shift in balance between PD-L1 and MICA correlated with enhanced activation of NKG2D receptor-expressing immune cells, evidenced by increased IFN-γ secretion.Conclusion: These findings suggest that NDV may exert antitumor effects by modulating the balance between inhibitory checkpoint molecules and stimulatory ligands, specifically through downregulation of PD-L1 and upregulation of MICA. This mechanism highlights the potential of NDV to enhance cytotoxic immune responses and supports its further development as a novel strategy in cancer immunotherapy.Keywords: Newcastle disease virus, PD-L1, MICA, NKG2D, interferons, oncolytic virotherapy
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a major subtype of secondary HLH and is increasingly recognized as a heterogeneous entity. However, the clinical differences between acute EBV-HLH (AEBV-HLH) and chronic active EBV infection-associated HLH (CAEBV-HLH) have not been systematically characterized. We conducted a scoping review of PubMed up to December 7, 2024, and identified 168 eligible articles involving 714 adult patients with EBV-HLH, including 584 with AEBV-HLH and 130 with CAEBV-HLH. Epidemiologic features, clinical manifestations, treatment patterns, and prognostic factors were summarized and compared between the two subgroups. Patients with AEBV-HLH showed more severe HLH-related abnormalities, including lower blood counts and higher ferritin, triglyceride, lactate dehydrogenase, and plasma EBV-DNA levels, whereas central nervous system involvement was more frequent in CAEBV-HLH. The median overall survival was significantly longer in CAEBV-HLH (8.9 months) than AEBV-HLH (2.4 months, P=0.005). In the overall cohort, ferritin >5000 μg/L, soluble CD25 >10000 U/mL, EBV-DNA >10000 copies/mL, and receiving hematopoietic stem cell transplantation (HSCT) were independently associated with better overall survival. In subgroup analyses, soluble CD25, EBV-DNA, and HSCT remained independent predictors in AEBV-HLH, whereas undergoing HSCT was the only independent prognostic factor in CAEBV-HLH. These findings support distinct clinical and prognostic characteristics between AEBV-HLH and CAEBV-HLH, especially in adults. AEBV-HLH is characterized by a more fulminant inflammatory presentation, whereas CAEBV-HLH more often follows a chronic course with greater extensive organ. HSCT appears to be central to long-term outcome in both subtypes.
Background:Nivolumab is used as a second-line treatment for pleural mesothelioma (PM); however, predictive or prognostic biomarkers remain unclear. We aimed to identify factors associated with survival in nivolumab-treated PM patients. Methods:This retrospective, multi-institutional cohort study included patients with PM who received nivolumab monotherapy as a second-line or later treatment at 18 hospitals in Japan. We evaluated associations of progression-free survival (PFS) and overall survival (OS) with baseline clinical variables, protein expression in tumor tissue specimens obtained before first-line therapy by immunohistochemical (IHC), and tumor mutational and copy-number profiles detected by next-generation sequencing (NGS). Results:Fifty-five patients were enrolled, with evaluable IHC in 42 and NGS in 33. V-domain immunoglobulin suppressor of T-cell activation (VISTA) expression was classified as high or low using a cutoff of 10% VISTA-positive tumor cells. High VISTA expression (n=35) was significantly associated with improved PFS and OS compared with low expression (n=7) (PFS: median, 5.1 vs 2.4 months, p = 0.001; OS: median, 12.8 vs 4.3 months, p = 0.007). Multivariate analysis confirmed high VISTA expression as an independent predictor of prolonged PFS and OS (PFS: hazard ratio [HR] 0.14, p < 0.001; OS: HR 0.38, p = 0.044). Conclusion:Low tumor-cell VISTA expression was associated with poorer outcomes following nivolumab treatment; however, independent validation in prospective studies with a comparator arm is required before VISTA expression can be used to guide treatment selection. These findings support further investigation of biomarkers for combination strategies such as nivolumab-ipilimumab or chemoimmunotherapy in PM.
Mitura-Lesiuk M, Najda P, Rdzanek O, et al. Immunotargets Ther. 2026;15:603087. https://doi.org/10.2147/ITT.S603087 The following article has been removed from the Dove Medical Press journal, Immunotargets and Therapy: Mirua-Lesiuk M, Najda P, Rdzanek O, Bogucka J, Różycka K, Dubaj M, and Zawitkowska J, “Blinatumomab for Pediatric High-Risk B-Cell Precursor Acute Lymphoblastic Leukemia: Safety, MRD Response and Survival in a Single-Center Retrospective Cohort” (https://doi.org/10.2147/ITT.S603087). Published online: 24 April 2026 This article has been removed in accordance with journal editorial policies.
