As members of the immune checkpoint family, PD-1 and its ligand PD-L1 play critical roles in maintaining the balance between autoimmunity and tolerance. The interaction of PD-1/PD-L1 is also involved in tumor evasion inside the tumor microenvironment, caused by reduced T cell activation, proliferation, cytotoxic secretion, and survival. Previous research has shown that the expression level of PD-1/PD-L1 may be regulated by ubiquitin-mediated proteasome degradation, which is an important mode of post-translational modification (PTM). PD-1/PD-L1 ubiquitin modification research in tumor immunotherapy is the subject of the present review, which aims to assess the most recent developments in this area. We offer a short explanation of PD-1/PD-L1 as well as some basic background information on the UPS system and discuss many routes that target E3s and DUBs, respectively, in the regulation of PD-1/PD-L1 in tumor immunotherapy. In addition, we offer numerous innovative prospective research areas for the future, as well as novel immunotherapy concepts and ideas. Taken together, the information compiled herein should serve as a comprehensive repository of information about tumor immunotherapy that is currently available, and it should be useful in the design of future studies, as well as the development of potential targets and strategies for future tumor immunotherapy.
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http://dx.doi.org/10.1016/j.gendis.2022.01.002 | DOI Listing |
J Hematol Oncol
January 2025
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.
View Article and Find Full Text PDFMol Cancer
January 2025
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, China.
Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age of onset. In recent years, there has been increasing recognition of the significance of tRNA-derived small RNAs (tsRNAs), encompassing tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, and epigenetics has gradually come to light.
View Article and Find Full Text PDFJ Transl Med
January 2025
Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.
View Article and Find Full Text PDFCancer Cell Int
January 2025
Department of Neurosurgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
The tertiary lymphoid structure (TLS) is recognized as a potential prognosis factor for breast cancer and is strongly associated with response to immunotherapy. Inducing TLS neogenesis can enhance the immunogenicity of tumors and improve the efficacy of immunotherapy. However, our understanding of TLS associated region at the single-cell level remains limited.
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