PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8 and CD4 T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both directly and indirectly.
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http://dx.doi.org/10.15698/cst2019.10.201 | DOI Listing |
Eur J Nucl Med Mol Imaging
October 2024
Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, 100191, China.
Purpose: In order to maximize synergistic effect of targeted radionuclide therapy (TRT) and immune checkpoint blockade (ICB) as well as reduce the toxicity, we pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy.
Methods: As a novel targeted radiotherapeutic agent, Lu-AB-3PRGD targeting integrin αβ was developed to achieve sustained antitumor effect by introducing an albumin binder (AB) into the structure of 3PRGD. The Lu-AB-3PRGD TRT as well as different types of combination therapies of Lu-AB-3PRGD TRT and anti-PD-L1 ICB were performed in animal models.
APMIS
December 2024
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Like their natural counterparts, chimeric antigen receptor-engineered cells are prone to suppression by inhibitory signals, such as PD-L1, expressed by tumors or suppressor cells in the tumor microenvironment. Consequently, they become impaired, resulting in immune cell exhaustion, tumor progression, and resistance to other therapies. In this study, we developed an anti-PD-L1-CAR NK cell with efficient activity and a notable PD-L1-specific response toward tumor cell lines.
View Article and Find Full Text PDFJ Med Chem
November 2024
International Joint Research Center for Tumor Precision Medicine of Shaanxi Province and Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China.
Despite the considerable achievements of antibodies targeting PD-1/PD-L1 in cancer immunotherapy, limitations in antitumor immune response and pharmacokinetics hinder their clinical adoption. Small molecules toward PD-L1 degradation signifies an innovative avenue to modulate PD-1/PD-L1 axis. Herein, we unveil a comprehensive engineering involving the development of new PD-L1 degraders based on the berberine (BBR) and palmatine (PMT) bioactive frameworks and explore their translational potential for cancer immunotherapy using a peptide-drug conjugate strategy.
View Article and Find Full Text PDFMol Imaging
July 2024
Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Background: Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases.
Objectives: To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors.
Eur J Nucl Med Mol Imaging
October 2024
Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
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