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    BIOMARKER:

    PD-L1 deletion

    i
    Other names: PD-L1, CD274, HPD-L1, PD-L1, B7H1, PDL1, Programmed death ligand 1, B7-H1, B7-H, PDCD1L1, PDCD1LG1, PDCD1 Ligand 1, B7 homolog 1, CD274 Antigen, Programmed cell death 1 ligand 1, CD274 molecule
    Entrez ID:
    29126
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    1m
    Nuclear PD-L1 compartmentalization suppresses tumorigenesis and overcomes immunocheckpoint therapy resistance in mice via histone macroH2A1. (PubMed, J Clin Invest)
    Importantly, LA treatment synergized with PD-1 antibody and overcame immune checkpoint blockade (ICB) resistance, which likely resulted from nPD-L1-increased MHC-I expression and sensitivity of tumor cells to interferon-γ. These findings offer a conceptual advance for PD-L1 function and suggest LA as a promising therapeutic option for overcoming ICB resistance.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • IFNG (Interferon, gamma)
    |
    PD-L1 expression • PD-L1 deletion
    1year
    PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma. (PubMed, Nat Cancer)
    Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1-mutated T-NHL and identify PD-1 as regulator of AP-1 activity.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1)
    |
    PD-L1 deletion • PD-L1 mutation
    over2years
    siRNA targeting PD-L1 delivered with attenuated Salmonella enhanced the anti-tumor effect of lenvatinib on mice bearing Hepatocellular carcinoma. (PubMed, Int Immunopharmacol)
    Furthermore, the combination treatment increased the number of granzyme B T cells, indicating a significantly improved anti-tumor immunity in mice. Therefore, this combination might be a potential novel strategy for HCC treatment.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1) • GZMB (Granzyme B)
    |
    VEGFA expression • PD-L1 deletion
    |
    Lenvima (lenvatinib)
    over2years
    A Global Study to Assess the Effects of Durvalumab with Oleclumab or Durvalumab with Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC-9) Ensayo mundial para evaluar los efectos de Durvalumab con Oleclumab o Durvalumab con Monalizumab tras la quimiorradioterapia simultánea en pacientes con cáncer de pulmón no microcítico irresecable en estadio III (PACIFIC-9) (clinicaltrialsregister.eu)
    P3, N=1670, Ongoing, AstraZeneca AB
    New P3 trial • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • EGFR mutation • EGFR wild-type • ALK mutation • ALK wild-type • EGFR wild-type + ALK wild-type • PD-L1 deletion
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    almost3years
    Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization. (PubMed, Sci Rep)
    This was further confirmed with flow cytometry that showed an increase in the M1 markers Ly6C + and CD80 +, and a decrease in the M2 marker CD206 + both in vitro and in vivo. Utilizing dual-sgRNAs and an HDR template with the CRISPR/Cas9 gene-editing system is a promising avenue for the treatment of GBM.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TNFA (Tumor Necrosis Factor-Alpha) • IL4 (Interleukin 4) • MRC1 (Mannose Receptor C-Type 1)
    |
    PD-L1 deletion
    almost3years
    Inhibition of myeloid PD-L1 suppresses osteoclastogenesis and cancer bone metastasis. (PubMed, Cancer Gene Ther)
    All these alterations result in heightened anti-tumor immunity in the cancer microenvironment. Our findings support PD-L1 antibody as a potent therapy for bone metastasis of breast cancer and melanoma by simultaneously suppressing osteoclast and enhancing immunity.
    Journal
    |
    IFNG (Interferon, gamma)
    |
    PD-L1 expression • PD-L1 deletion
    almost3years
    CD274 (PD-L1) Copy Number Changes (Gain) & Response to Immune Checkpoint Blockade Therapy in Carcinomas of the Urinary Tract. (PubMed, Bladder Cancer)
    Of the 9 patients whose tumors had PD-L1 copy number losses, 4 received immunotherapy with 3 experiencing disease progression. PD-L1 copy number alterations may serve as potential biomarkers of response to immunotherapy in urothelial carcinoma patients, if validated in larger cohorts.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 amplification • PD-L1 deletion
    over3years
    N-methyladenosine-modified circIGF2BP3 inhibits CD8 T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer. (PubMed, Mol Cancer)
    Our results reveal the function of circIGF2BP3 in causing immune escape from CD8 T cell-mediated killing through a decrease in PD-L1 ubiquitination and subsequent proteasomal degradation by stabilizing OTUB1 mRNA in a PKP3-dependent manner. This work sheds light on a novel mechanism of PD-L1 regulation in NSCLC and provides a rationale to enhance the efficacy of anti-PD-1 treatment in NSCLC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • MIR328 (MicroRNA 328) • METTL3 (Methyltransferase Like 3)
    |
    IGF2 elevation • IGFBP3 elevation • PD-L1 deletion