90K is a widely expressed, secreted 90 kDa human serum protein found both in normal individuals and at elevated levels in the serum of cancer patients. Functional characterization revealed stimulatory effects of 90K on immune defense systems, such as natural killer and lymphokine-activated killer cell activity. Recently, experiments have shown that 90K expression in several tumor cell lines inversely correlates with tumor formation in athymic mice. The mechanism of this tumor suppressive effect is unknown. In the present study, we evaluated the ability of 90K to affect the expression of MHC class I molecules in the human breast cancer cell line EVSA-T. Treatment with 90K (1-50 micrograms/ml) caused the levels of MHC class I expression to increase approximately sixfold above control levels, as measured by flow cytometry. IFN-gamma was used as a positive control and yielded increased expression of MHC class I molecules approximately 8 times over control levels. These data demonstrate that 90K can directly affect the expression of molecules that are engaged in protective antitumor response.
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http://dx.doi.org/10.1006/bbrc.1996.1219 | DOI Listing |
FASEB J
January 2025
Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe liver inflammation and fibrosis due to an imbalanced immune response caused by enhanced bacterial components. The progression of MASH is closely linked to increased permeability of intestinal mucosal barrier facilitating enter of bacterial components into hepatic portal venous system. B cells are important immune cells for adaptive responses and enhance hepatic inflammation through cytokine production and T cell activation.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Dermatology and Allergy, University Hospital of Munich, Ludwig-Maximilian-University, Munich, Germany.
Background: Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. RECQL4, a RecQ-like helicase, plays a central role in DNA replication and repair as part of the DNA damage response, a pathway implicated in enhancing efficacy of immune checkpoint inhibitor (ICI) therapies. However, its role in patient response to ICI remains unclear.
View Article and Find Full Text PDFCancer Immunol Res
January 2025
Vanderbilt University, Nashville, TN, United States.
Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicate detection by immunohistochemistry.
View Article and Find Full Text PDFBiomaterials
January 2025
Department of Biomedical Engineering, University of Iowa, Iowa City, IA, 52242, USA; Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USA. Electronic address:
Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA.
The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary.
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