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Antibody blockade of the PSGL-1 immune checkpoint enhances T-cell responses to B-cell lymphoma.
Leukemia
January 2025
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Despite advancements in cancer immunotherapy, most lymphomas remain unresponsive to checkpoint inhibitors. P-selectin glycoprotein ligand-1 (PSGL-1), recently identified as a promoter of T-cell exhaustion in murine melanoma models, has emerged as a novel immune checkpoint protein and promising immunotherapeutic target. In this study, we investigated the potential of PSGL-1 antibody targeting in B-cell lymphoma.
View Article and Find Full Text PDFA Case of Extranodal NK/T-cell Lymphoma Infiltrating Kidneys, Presenting With Hematuria and Proteinuria With False-Positive Serum Anti-proteinase 3, and Mimicking Granulomatosis With Polyangiitis.
Cureus
December 2023
Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, THA.
We report a case of misdiagnosed extranodal NK/T-cell lymphoma, nasal type, mimicking granulomatosis with polyangiitis (GPA). A 30-year-old male presented with chronic non-resolving right paranasal sinusitis for two years accompanied by multiple generalized cutaneous nodules, and subnephrotic-range proteinuria. Biopsies from skin lesions and paranasal sinuses demonstrated leukocytoclastic vasculitis and necrotizing granulomatous inflammation, respectively.
View Article and Find Full Text PDFTIGIT is a key inhibitory checkpoint receptor in lymphoma.
J Immunother Cancer
June 2023
Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA
Background: PD-1 checkpoint blockade therapy (CBT) has greatly benefited patients with select solid tumors and lymphomas but has limited efficacy against diffuse large B-cell lymphoma (DLBCL). Because numerous inhibitory checkpoint receptors have been implicated in driving tumor-specific T cell dysfunction, we hypothesized that combinatorial CBT would enhance the activity of anti-PD-1-based therapy in DLBCL. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a coinhibitory receptor expressed on dysfunctional tumor-infiltrating T cells, and TIGIT blockade has demonstrated encouraging activity in combination with PD-1 blockade in murine tumor models and in clinical studies.
View Article and Find Full Text PDFExpression of Sirt1 and FoxP3 in classical Hodgkin lymphoma and tumor infiltrating lymphocytes: Implications for immune dysregulation, prognosis and potential therapeutic targeting.
Int J Clin Exp Pathol
October 2016
Department of Pathology and Laboratory Medicine, UTHealth-Medical School at Houston Houston, USA.
Background: Hodgkin Reed-Sternberg (HRS) cells may promote differentiation of CD4+ naïve T cells toward both FoxP3+ T regulatory (Treg) cells and TIA-1+ cytotoxic T lymphocytes (CTL). Previous studies suggest that an overabundance of cytotoxic TIA-1+ cells in relation to FoxP3+ T reg cells portends unfavorable outcomes in classical Hodgkin lymphoma (cHL), raising the possibility that its pathogenesis may be related to immune dysregulation. Sirt1 deacetylates FoxP3 and leads to decreased Treg functionality.
View Article and Find Full Text PDFMesenchymal stromal cells support the viability and differentiation of follicular lymphoma-infiltrating follicular helper T-cells.
PLoS One
August 2015
James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States of America.
The biology of follicular lymphoma (FL) is largely dictated by the immune-effector and stromal cells that comprise its tumor microenvironment. FL-infiltrating T-cell populations that are thought to be fundamental to FL biology are follicular helper T-cells (TFH), follicular regulatory T-cells (TFR), a recently described population that regulates TFH activity, and regulatory T-cells (Treg). These T-cell populations have dynamic interactions with mesenchymal stromal cells (MSCs) in the tumor microenvironment.
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