- |||||||||| Keytruda (pembrolizumab) / Merck (MSD)
Journal: 1,5-Disubstituted tetrazoles as PD-1/PD-L1 antagonists. (Pubmed Central) - Apr 26, 2024 The progress in cancer survival and treatment has witnessed a remarkable transformation through the innovative approach of targeting the inhibitory immune checkpoint protein PD-1/PD-L1 complex by mAbs, e.g. pembrolizumab (Keytruda)...Supported by a cocrystal structure with PD-L1, these inhibitors underwent biophysical testing, including HTRF and protein NMR experiments, resulting in the identification of potent candidates with sub-micromolar PD-L1 affinities. This finding opens opportunities to the further development of a new class of PD-L1 antagonists, holding promise for improved cancer immunotherapy strategies.
- |||||||||| Journal, Tumor cell: Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer. (Pubmed Central) - Apr 25, 2024
In vivo fluorescence imaging and H&E staining showed that the nanomedicine was mainly retained in the tumor site and had no significant toxic side effects on other major organs. The anti-PD-L1/TCL@Lipo-PEG prepared in this study has high efficacy and good biosafety in alleviating the progression of Lynch syndrome-associated colon cancer, and it is expected to be a therapeutic candidate for Lynch syndrome-associated colon cancer.
- |||||||||| PD-L1 deletion on T cells results in a pro-tumorigenic environment (Exhibit Hall F1; Poster Board Number: B122) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1006;
These findings correlated with higher expression of PD-L1 on TAMs, M-MDSC, and PMN-MDSC. Our results indicate that PD-L1 ablation on CD8+ T cells confers an activated phenotype which leads to the generation of immunosuppressive myeloid cells in the TME and may be involved in adaptive immune resistance during checkpoint immunotherapy.
- |||||||||| PD-L1 deletion on T cells results in a pro-tumorigenic environment (Room W178) - Mar 22, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_513;
These findings correlated with higher expression of PD-L1 on TAMs, M-MDSC, and PMN-MDSC. Our results indicate that PD-L1 ablation on CD8+ T cells confers an activated phenotype which leads to the generation of immunosuppressive myeloid cells in the TME and may be involved in adaptive immune resistance during checkpoint immunotherapy.
- |||||||||| Conditional reprogramming of urine-derived bladder cancer cells: A model for precision medicine (Exhibition area) - Oct 6, 2023 - Abstract #ESMOAsia2023ESMO_Asia_776;
Conclusions Our study demonstrates the successful establishment of a reliable and patient-specific bladder cancer cell model derived from urine samples which serve to guide anti-tumor drugs and immunotherapeutic interventions. The findings underscore the clinical utility and translational potential of urine-derived cells for personalized bladder cancer management.
- |||||||||| Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker, Tumor cell: A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells. (Pubmed Central) - Aug 9, 2023
In addition, the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients. In conclusion, as a novel personalized urine-detection method, UBC-PD-L1 may provide a rapid, accurate, and non-invasive tool for monitoring tumor progression, predicting therapeutic responses, and helping improve BLCA clinical treatment in
- |||||||||| The Ovarian Oncobiome Regulates the Immune Checkpoint Molecule PD-L1 In Vitro. (Great Hall 3&4, Foyer Level) - Mar 20, 2023 - Abstract #SRI2023SRI_791;
The inflammatory microenvironment regulates the sensibility to bacteria possibly through modulation of TLR2 or TLR4 expression or function. However, a bacteria-mediated PD-L1 upregulation was also observed in the absence of TLR regulation.
- |||||||||| bleomycin / Generic mfg.
Journal, PD(L)-1 Biomarker, IO biomarker: PD-L1 upregulation promotes drug-induced pulmonary fibrosis by inhibiting vimentin degradation. (Pubmed Central) - Jan 1, 2023 Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs)...Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.
- |||||||||| Review, Journal: Divergent roles of PD-L1 in immune regulation during ischemia-reperfusion injury. (Pubmed Central) - Dec 9, 2022
This review briefly describes the immune response during I/R injury and how PD-L1 is involved in its regulation by focusing on findings from various I/R models. Despite the limited number of studies in this field of research, PD-L1 has shown sufficient potential as a clinical therapeutic target.
- |||||||||| Programmed Death Ligand 1 Is Released in Platelet-Derived Extracellular Vesicles () - Nov 29, 2022 - Abstract #ASH2022ASH_6966;
Platelet EV counts increased substantially after platelet stimulation with ADP (120 x 108/ml), or thrombin (74 x 108/ml) compared to unstimulated platelets (31 x 108/ml).Conclusion :These pilot studies suggest that platelet activation results in release of EV containing PD-L1. Studies are in progress to determine whether these EV may regulate responses or toxicities of ICI through transfer of PD-L1 to other cell types, or other mechanisms.
- |||||||||| Journal, PD(L)-1 Biomarker, IO biomarker: Nanohydroxyapatite Stimulates PD-L1 Expression to Boost Melanoma Combination Immunotherapy. (Pubmed Central) - Nov 1, 2022
The results confirmed that the combinational strategy effectively suppressed tumorigenesis and tumor growth, recovered the abnormal lactate dehydrogenase, aspartate transaminase, and alanine aminotransferase indicators, and significantly elongated the life span of a tumor-bearing mouse. The substantive progress mainly derived from nHA-induced T cell infiltration reinforcement in a tumor site and CD8 T cell polarization in spleen, implying that nHA might function as an immunomodulator for melanoma immunotherapy.
- |||||||||| thyroxine / Generic mfg.
Journal, PD(L)-1 Biomarker, IO biomarker: Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway. (Pubmed Central) - Oct 22, 2022 Thyroid hormone as L-thyroxine (T) stimulates cancer cell proliferation via a receptor on integrin αvβ3 of plasma membranes...Suppression PD-L1 expression by shRNA blocked not only expression of PD-L1 and β-catenin but also signal transduction, proliferative gene expressions, and cancer cell growth. In summary, thyroxine via integrin αvβ3 activated ERK1/2 and STAT3 to stimulate the PD-L1-dependent and β-catenin-related growth in oral cancer cells.
- |||||||||| 5-fluorouracil / Generic mfg.
Journal, PD(L)-1 Biomarker, IO biomarker: ATXN2-Mediated PI3K/AKT Activation Confers Gastric Cancer Chemoresistance and Attenuates CD8 T Cell Cytotoxicity. (Pubmed Central) - Oct 11, 2022 In conclusion, our study reveals the important roles of the SP1/ATXN2/PI3K-AKT/BCL2L1 signalling pathway in GC chemoresistance and of the SP1/ATXN2/PI3K-AKT/PD-L1 signalling pathway in GC immunotherapy. Our findings provide new theories and experimental references for overcoming chemotherapy resistance in GC and enhancing the efficacy of immunotherapy for GC.
- |||||||||| Journal, PD(L)-1 Biomarker, IO biomarker: HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling. (Pubmed Central) - Sep 20, 2022
Our findings demonstrated that soluble rHSP90α increased the resistance of normal human monocytes to apoptosis and converted them into immunosuppressive MDSC via TLR4 signaling that stimulated PD-L1 and IDO-1 expression. Furthermore, patients with melanoma with high concentrations of HSP90α displayed increased PD-L1 expression on M-MDSC and reduced PFS after ICI therapy, suggesting HSP90α as a promising therapeutic target for overcoming immunosuppression in melanoma.
- |||||||||| Tecentriq (atezolizumab) / Roche
Journal, PD(L)-1 Biomarker, IO biomarker: PD-L1 CAR effector cells induce self-amplifying cytotoxic effects against target cells. (Pubmed Central) - Mar 24, 2022 In summary, our studies show that CAR-effector cells trigger the expression of PD-L1 on target cells, which in case of PD-L1-CAR results in the unique self-amplification phenomenon. This self-amplifying effect could be responsible for the enhanced cytotoxicity of PD-L1-CAR T cells against both malignant and non-malignant cells and implies extensive caution in introducing PD-L1-CAR strategy into clinical studies.
- |||||||||| Tecentriq (atezolizumab) / Roche
Tumor-reactive and anti-PD-L1 co-stimulated killer cells (TRACK-NK) for immunotherapy of non-small cell lung cancer (Section 18) - Mar 9, 2022 - Abstract #AACR2022AACR_2484; In summary, our studies using human allogeneic off-the-shelf TRACK-NK cells proved to be safe and non-toxic, demonstrated enhanced cytotoxicity against NSCLC in vitro and enhanced control of tumor growth in vivo, further improved with atezolizumab. As the intravenous infusion of activated NK cells naturally traffic to lung, our TRACK-NK platform will move forward to the clinic for the treatment of relapsed and refractory NSCLC patients.
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