Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. Current challenges associated with the enhancement of ICI effects are increasing the fraction of responding patients through personalized combinations of multiple ICIs and overcoming acquired resistance. This requires a complete overview of the anti-tumor immune response, which depends on a complex interplay between innate and adaptive immune cells with the tumor microenvironment. The NKG2A was revealed to be a key immune checkpoint for both Natural Killer (NK) cells and T cells. Monalizumab, a humanized anti-NKG2A antibody, enhances NK cell activity against various tumor cells and rescues CD8 αβ T cell function in combination with PD-1/PD-L1 blockade. In this review, we discuss the potential for targeting NKG2A expressed on tumor-sensing human γδ T cells, mostly on the specific Vδ2 T cell subset, in order to emphasize its importance and potential in the development of new ICI-based therapeutic approaches.
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http://dx.doi.org/10.3390/cancers15041264 | DOI Listing |
Sci Rep
January 2025
Department of Chemistry and Biochemistry, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~ 400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic for the treatment of cancer. Unfortunately, detrimental side effects were observed and hindered the clinical development of pan-Hsp90 inhibitors.
View Article and Find Full Text PDFNat Commun
January 2025
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.
Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.
View Article and Find Full Text PDFCancer Lett
January 2025
Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address:
Immune checkpoint blockade (ICB) combined with radiotherapy (RT) has improved patients survival, but also increased the risk of pulmonary adverse effects (AEs). Therefore, to explore potential drug targets for interstitial lung disease (ILD), we investigated the interaction of ICB and RT in pulmonary AEs using the disproportionality analysis and COX regression. Genome-wide association studies, transcriptome analysis, and vivo models highlighted the role of programmed death-ligand-1 (PD-L1) in ILD.
View Article and Find Full Text PDFBMC Cancer
January 2025
Young Academy of Gynecologic Oncology (JAGO), Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO), Berlin, Germany.
Background: The integration of immune checkpoint inhibitors (ICIs) into routine gynecologic cancer treatment requires a thorough understanding of how to manage immune-related adverse events (irAEs) to ensure patient safety. However, reports on real-world clinical experience in the management of ICIs in gynecologic oncology are very limited. The aim of this survey was to provide a real-world overview of the experiences and the current state of irAE management of ICIs in Germany, Switzerland, and Austria.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Non-small cell lung cancer (NSCLC) remains a dire disease being the first cause of cancer death among both genders. Early-stage NSCLC often has better treatment outcomes despite it being a highly heterogeneous disease. So far, the neo-adjuvant chemotherapy strategies have led to a small benefit with an improvement of 5% in overall survival as an absolute benefit.
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