Increased production of immunosuppressive IL-10 by non-small cell lung cancer (NSCLC) and increased plasma IL-10 concentrations in NSCLC-patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL-2 secretion in NSCLC-patients. We now analyzed the influence of IL-2 suppression on survival in NSCLC-patients and influence of IL-10 on IL-2 secretion. The correlation of the IL-2-concentration in whole blood cell cultures from 90 NSCLC-patients at the time of diagnosis to survival was analyzed by using crit-level, the Kaplan-Meier method and the log-rank test. IL-2 secretion capacity at the time of diagnosis significantly influenced survival in NSCLC-patients. With a cut-off value for IL-2 of 1100 pg/ml, the difference in survival was significant with a P-value of 0.014 in the whole patient group. In the subgroup of surgically treated patients (n=33), survival was different with a P-value of 0.011. Moreover, secretion of IL-2 was inhibited in a dose-dependent manner upon addition of IL-10 in whole blood cell cultures from normal individuals. Thus, suppression of IL-2 secretion is predictive for survival of NSCLC-patients and may be mediated by tumor-derived IL-10.
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http://dx.doi.org/10.1016/s0169-5002(01)00350-6 | DOI Listing |
Front Immunol
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Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage.
View Article and Find Full Text PDFBioorg Med Chem
January 2025
Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, #555 Zu Chong Zhi Road, Shanghai 201203 China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Qixia District, Nanjing 210023 China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024 China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:
Hematopoietic progenitor kinase 1 (HPK1) has emerged as a promising target for cancer immunotherapy due to its critical role as a negative regulator of T cell receptor (TCR) signaling. Despite this potential, no HPK1 inhibitors have been approved for cancer treatment, underscoring the need for structurally novel inhibitors. Herein, we describe the design, synthesis and biological evaluation of a series of potent HPK1 inhibitors based on our previously identified hit 9.
View Article and Find Full Text PDFBMC Biol
January 2025
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Background: Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor immune evasion. Therefore, screening of immune checkpoint inhibitors (ICIs) targeting the CD96/PVR pathway will provide promising candidates for tumor immunotherapy.
View Article and Find Full Text PDFMol Immunol
January 2025
Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Master Program of Pharmaceutical Manufacture, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. Electronic address:
The immunoglobulin E (IgE) receptor FcεRI (Fc epsilon RI) plays a crucial role in allergic reactions. Recent studies have indicated that the interaction between FcεRIβ and the downstream protein phospholipase C beta 3 (PLCβ3) leads to the production of inflammatory cytokines. The aim of this study was to develop small molecules that inhibit the protein-protein interactions between FcεRIβ and PLCβ3 to treat allergic inflammation.
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