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LAG Time in the Era of Immunotherapy-New Molecular Insights Into the Immunosuppression Mechanism of Lymphocyte Activation Gene-3.
Immunol Rev
March 2025
Department of Immunology, Moffitt Cancer Center, Tampa, Florida, USA.
The immune checkpoint receptor lymphocyte activation gene-3 (LAG3) inhibits T-cell activation and was recently validated as a target for cancer immunotherapy. Despite its emergence as a therapeutic target, a lack of molecular-level insight has obscured our understanding of the LAG3 immunosuppression mechanism. This review highlights a series of breakthroughs that have illuminated fundamental aspects of LAG3 molecular biology.
View Article and Find Full Text PDFCharacteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases.
FEBS Lett
January 2025
School of Science, STEM College, RMIT University, Melbourne, Australia.
The Kelch protein superfamily is an evolutionary conserved family containing 63 alternate protein coding members. The superfamily is split into three subfamilies: Kelch like (KLHL), Kelch-repeat and bric-a-bracs (BTB) domain containing (KBTBD) and Kelch domain containing protein (KLHDC). The KLHDC subfamily is one of the smallest within the Kelch superfamily, containing 10 primary members.
View Article and Find Full Text PDFmRNA vaccine-induced SARS-CoV-2 spike-specific IFN-γ and IL-2 T-cell responses are predictive of serological neutralization and are transiently enhanced by pre-existing cross-reactive immunity.
J Virol
January 2025
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Unlabelled: The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) and interleukin-2 (IL-2) T-cell responses and neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity on cellular and humoral responses to vaccination were additionally assessed.
View Article and Find Full Text PDFViral influencers: deciphering the role of endogenous retroviral LTR12 repeats in cellular gene expression.
J Virol
January 2025
Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.
The human genome is like a museum of ancient retroviral infections. It contains a large number of endogenous retroviruses (ERVs) that bear witness to past integration events. About 5,000 of them are so-called long terminal repeat 12 (LTR12) elements.
View Article and Find Full Text PDFThe impact of CD3ζ ITAM multiplicity and sequence on CAR T-cell survival and function.
Front Immunol
January 2025
Department of Pathology, University of Utah, Salt Lake City, UT, United States.
Introduction: Chimeric antigen receptor (CAR) expressing T-cells have shown great promise for the future of cancer immunotherapy with the recent clinical successes achieved in treating different hematologic cancers. Despite these early successes, several challenges remain in the field that require to be solved for the therapy to be more efficacious. One such challenge is the lack of long-term persistence of CD28 based CAR T-cells in patients.
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