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    BIOMARKER:

    PD-L1 amplification

    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
    2ms
    Primary pulmonary histiocytic sarcoma with high PD-L1 expression benefited from immunotherapy: A case report and bioinformatic analysis. (PubMed, Clin Respir J)
    Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 overexpression • PD-L1 amplification
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • doxorubicin hydrochloride • cyclophosphamide • vincristine
    2ms
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
    |
    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab)
    2ms
    Unraveling the Significance of MET Focal Amplification in Lung Cancer: Integrative NGS, FISH, and IHC Investigation. (PubMed, Mod Pathol)
    Notably, a strong correlation was observed between focal amplification and PD-L1 expression, indicating potential therapeutic implications with combined MET inhibitor and immunotherapy for patients with both alterations. Our findings provide insights into the molecular complexity and clinical relevance of METamp in lung cancer, highlighting the role of MET focal amplification as an oncogenic driver and its feasibility as a primary biomarker to further investigate the clinical activity of MET inhibitors in future studies.
    Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    PD-L1 expression • MET amplification • MET overexpression • MET expression • PD-L1 amplification
    2ms
    Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1. (PubMed, Phytomedicine)
    This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8)
    |
    PD-L1 expression • PD-L1 amplification
    2ms
    Molecular and Treatment Characteristics of SMARCB1 or SMARCA4-Deficient Undifferentiated Tumor: Retrospective Case Series. (PubMed, Cancer Res Treat)
    However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.
    Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
    |
    PD-L1 amplification
    3ms
    MoST-TAP: Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients (clinicaltrials.gov)
    P2, N=96, Recruiting, Omico | Not yet recruiting --> Recruiting
    Enrollment open • Pan tumor • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • PD-L1 amplification
    |
    Tecentriq (atezolizumab) • Pegasys (pegylated interferon α -2a) • tiragolumab (RG6058)
    4ms
    SWOG S1609: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors (clinicaltrials.gov)
    P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> May 2026 | Trial primary completion date: Oct 2024 --> May 2026
    Trial completion date • Trial primary completion date
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 overexpression • PD-L1 amplification
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)
    5ms
    The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression. (PubMed, Cancer Med)
    The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDH1 (Cadherin 1)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 expression • ARID1A mutation • MYC amplification • PD-L1 amplification • HER-2 amplification + PD-L1 expression • CCNE1 mutation
    5ms
    High Prevalence of MYD88 and CD79B Mutations and PD-L1 Alterations in Bone Marrow Large B Cell Lymphoma Associated with Hemophagocytic Lymphohistiocytosis (ASH 2023)
    To the best of our knowledge, this is the first study exploring the molecular genetics of bone marrow large B cell lymphoma with HLH. Our study suggesting bone marrow large B cell lymphoma with HLH showed frequent MYD88/CD79B and PD-L1 alterations. Our study provided clues for the pathogenesis of bone marrow large B cell lymphoma with HLH and identified potential druggable targets for future clinical trials.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • IGH (Immunoglobulin Heavy Locus) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CD79B (CD79b Molecule) • CD5 (CD5 Molecule) • PIM1 (Pim-1 Proto-Oncogene) • IRF4 (Interferon regulatory factor 4)
    |
    CD79B mutation • PD-L1 amplification • CD79B mutation • BCL6 translocation
    5ms
    Anti-tumor effect of PD-L1-targeting antagonistic aptamer-ASO delivery system with dual inhibitory function in immunotherapy. (PubMed, Cell Chem Biol)
    This chimera not only blocks PD-L1/PD-1 but also achieves targeted delivery of the conjugated ASO to reduce both surface PD-L1 and total PD-L1 expression. Compared with the single blockade, this chimera with the dual inhibitory function synergistically inhibits PD-L1 to amplify immunotherapeutic efficacy, providing a promising synergistic strategy for immunotherapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 amplification
    6ms
    Chromosome 9p Duplication Promotes T-Cell Exhaustion and Enhances Stem Cell Clonogenic Potential in JAK2-Mutant Myeloproliferative Neoplasms (ASH 2023)
    In conclusion, our comprehensive characterization of the molecular interplay between JAK2V617F and chromosome 9 alterations, along with their immunological implications due to PD-L1 hyperactivation, fills a critical knowledge gap and provides valuable insights into the disease progression of 9p-MPNs. Further analysis is ongoing to explore the associations between 9p duplication and hematological parameters in 9p-MPN patients for a better understanding of the clinical implications of this genetic abnormality in MPNs.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • JAK2 (Janus kinase 2) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD34 (CD34 molecule) • CD14 (CD14 Molecule) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
    |
    PD-L1 expression • PD-L1 amplification • JAK2 V617F • JAK2 mutation • JAK2 amplification
    6ms
    Macrophages Play a Key Role in Controlling Tumor Growth and Response to Immunotherapy in Primary Central Nervous System Lymphoma (ASH 2023)
    Blocking PD1 exhibits superior efficacy when macrophages are present, indicating T cells are not the only player in this tumoral scenario. As a result, our study suggests that a promising approach for treating primary CNS lymphomas would involve targeting both T cells and macrophages.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 amplification
    6ms
    SWOG S1609: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors (clinicaltrials.gov)
    P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
    Trial completion date • Trial primary completion date
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 overexpression • PD-L1 amplification
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)
    8ms
    Concurrent predictors of an immune responsive tumor microenvironment within tumor mutational burden-high breast cancer. (PubMed, Front Oncol)
    Along with MSI-H and PD-L1+, several biomarkers, including B2M mutation and CD274 amplification, may help predict ICI benefit amongst TMB-H tumors. Co-occurring biomarkers within TMB-H breast cancer warrant evaluation in larger cohorts for response or resistance to ICI to develop composite predictive biomarkers in MBC.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • CDH1 (Cadherin 1)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • HER-2 negative • HER-2 mutation • TMB-L • PD-L1 amplification • B2M mutation • CDH1 mutation
    |
    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    8ms
    MoST-TAP: Tiragolumab and Atezolizumab in Advanced Pan-cancer Patients (clinicaltrials.gov)
    P2, N=96, Not yet recruiting, Omico
    New P2 trial • Pan tumor • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • PD-L1 amplification
    |
    Tecentriq (atezolizumab) • Pegasys (pegylated interferon α -2a) • tiragolumab (RG6058)
    9ms
    Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity. (PubMed, J Clin Invest)
    In lymphoid tissues, the lack of host-tissue PD-L1 interaction with PD-1 reduced the inhibition of the GSH/Myc pathway despite reduced GSH production caused by STAT3 deficiency and allowed donor T cell functions that mediate GVL activity. Therefore, STAT3 deficiency in donor T cells augments PD-1 signaling-mediated inhibition of GSH/Myc pathways and augments dysfunction of T cells in GVHD target tissues while sparing T cells in lymphoid tissues, leading to prevention of GVHD while preserving GVL effects.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    PD-L1 amplification
    10ms
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    10ms
    Metabolic Intervention Liposome Boosted Lung Cancer Radio-Immunotherapy via Hypoxia Amelioration and PD-L1 Restraint. (PubMed, Adv Sci (Weinh))
    Then, TPP-LND is wrapped with liposomes to form TPP-LND@Lip nanoparticles. By doing this, TPP-LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD-L1 via enhancing the adenosine 5'-monophosphate-activated protein kinase activation. As expected, these well-designed economical TPP-LND@Lip nanoparticles are more effective than conventional anti-PD-L1 antibodies to some extent.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 expression • PD-L1 amplification
    10ms
    New Insights Into the Pathogenesis of T-Cell Lymphoma and How This May Guide Treatment (SOHO 2023)
    TFHLs, which frequently carry mutations of TET2, DNMT3A, RHOA and IDH2, rarely seen in combination in other PTCL, have a higher response rate to hypomethylating agents such as 5-azacytidine and histone deacetylase inhibitors such as romidepsin. Tumors harboring SVs or amplification of CD274 may show greater sensitivity to immune checkpoint inhibitors. Four tumor microenvironment subgroups defined by expression profiling alone, may represent immunotherapy biomarkers.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • JAK1 (Janus Kinase 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • JAK3 (Janus Kinase 3) • RHOA (Ras homolog family member A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • TBX21 (T-Box Transcription Factor 21) • TYK2 (Tyrosine Kinase 2) • DUSP22 (Dual Specificity Phosphatase 22) • GATA3 (GATA binding protein 3) • USP22 (Ubiquitin Specific Peptidase 22)
    |
    PD-L1 expression • TP53 mutation • ALK positive • DNMT3A mutation • ALK fusion • NOTCH1 mutation • CDKN2A deletion • TET2 mutation • CDKN2A mutation • RB1 deletion • PD-L1 amplification • ALK negative • STAT3 mutation
    |
    azacitidine • Istodax (romidepsin)
    10ms
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Not yet recruiting, German Cancer Research Center | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Apr 2029 --> Mar 2030
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TROP2 (Trophoblast Cell Surface Antigen 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    11ms
    IGH::CD274 (PD-L1) rearrangement in diffuse large B cell lymphoma and its therapeutic implication. (PubMed, EJHaem)
    DLBCL with PD-L1 overexpression is often resistant to R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone). Our patients responded to a combination of R-CHOP and a PD-1 inhibitor.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 overexpression • PD-L1 amplification
    |
    Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine
    1year
    Tantalum-Zirconium Co-Doped Metal-Organic Frameworks Sequentially Sensitize Radio-Radiodynamic-Immunotherapy for Metastatic Osteosarcoma. (PubMed, Adv Sci (Weinh))
    Furthermore, a combination of TZM, X-ray, and anti-PD-L1 treatments amplify antitumor immunotherapy and efficiently arrest osteosarcoma growth and metastasis. These results indicate that TZM is a promising radiosensitizer for the synergistic RT and immunotherapy of metastatic osteosarcoma.
    Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-1 (Programmed cell death 1) • CGAS (Cyclic GMP-AMP Synthase)
    |
    PD-L1 expression • PD-L1 amplification
    1year
    DART: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors (clinicaltrials.gov)
    P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 overexpression • PD-L1 amplification
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab)
    1year
    Non-autonomous enhancement of gPDL1 CAR-T annihilates TNBC development (AACR 2023)
    Despite the excellent anti-cancer activity, the atezolizumab-based chimeric antigen receptor (CAR) T cells showed a robust off-target effect. Overall, gPD-L1 CAR-T exhibits excellent anti-tumor activity against TNBCs, and it could be a promising immunotherapy tool to treat TNBCs in clinic. Furthermore, targeting glycosylation moiety on the tumor antigen is a novel approach to lessen CAR-T toxicity in patients.
    PD(L)-1 Biomarker • IO biomarker
    |
    IFNG (Interferon, gamma)
    |
    PD-L1 expression • PD-L1 amplification
    |
    Tecentriq (atezolizumab) • gPD-L1 CAR-T
    1year
    Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer. (PubMed, BMC Cancer)
    The prevalence of PD-L1 genetic alterations was relatively low in CRC, but the aberrations usually correlate with aggressive nature. The correlation between PD-L1 genetic alterations and tumor immune features was only observed in dMMR CRC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule)
    |
    PD-L1 expression • MSI-H/dMMR • PD-L1 amplification
    1year
    Tumor Microenvironment and Its Clinicopathologic and Prognostic Association in Cutaneous and Noncutaneous Angiosarcomas. (PubMed, Am J Clin Pathol)
    Our HTG analyses confirmed a high degree of tumor and microenvironment heterogeneity. Cutaneous ASs, ASs without MYC amplification, and ASs located in the head and neck area seem to be the most immunogenic subtypes in our series.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1)
    |
    PD-L1 expression • PD-L1 overexpression • MYC amplification • CD8 expression • PD-L1 amplification
    |
    HTG EdgeSeq Precision Immuno-Oncology Panel
    1year
    PD-L1 gene amplification and focality: relationship with protein expression. (PubMed, J Immunother Cancer)
    In conclusion, PD-L1 expression measured by IHC is influenced by PD-L1 amplification level and focality. Further correlation between amplification, focality, protein expression and therapeutic outcome for PD-L1 and other targetable genes warrants exploration.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 overexpression • PD-L1 amplification
    |
    PD-L1 IHC 22C3 pharmDx
    1year
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Not yet recruiting, German Cancer Research Center | Initiation date: Dec 2022 --> May 2023
    Trial initiation date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TROP2 (Trophoblast Cell Surface Antigen 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    over1year
    Diagnostic Accuracy of Slow-Capillary Endobronchial Ultrasound Needle Aspiration in Determining PD-L1 Expression in Non-Small Cell Lung Cancer. (PubMed, Adv Respir Med)
    These retrospective study shows that slow-pull capillary aspiration carries an excellent diagnostic accuracy, almost equal to that one reported in literature, supporting its use in EBUS-TBNA for PD-L1 testing in NSCLC.
    Journal • Endobronchial ultrasound • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 amplification
    over1year
    Clinical and molecular features of ATM and BRCA2 mutations in metastatic prostate cancer. (ASCO-GU 2023)
    ATM or BRCA2 mutations also predicted worse response to the AR-targeted abiraterone/enzalutamide therapies (HR 0.4, 0.3; CI 0.244-1.003, 0.172 – 0.6; P = 0.047, p < 0.001). We found that somatic ATM and BRCA2 mutations associated with differential OS outcomes, which may help tailor treatment decisions. At the molecular level, ATM- and BRCA2-mutated tumors exhibited differences in the landscape of co-occurring genomic and transcriptional features. These features unique to ATM or BRCA2 mutations can inform rationale for divergent treatment strategies and should be investigated.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Metastases
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • ALDH1A3 (Aldehyde Dehydrogenase 1 Family Member A3) • HES4 (Hes Family BHLH Transcription Factor 4)
    |
    TP53 mutation • BRCA2 mutation • TMB-H • ATM mutation • PD-L1 amplification • BRCA2 expression
    |
    MI Tumor Seek™
    |
    Xtandi (enzalutamide capsule) • abiraterone acetate
    over1year
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Active, not recruiting, Asan Medical Center | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
    |
    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab)
    over1year
    Prevalence of Predictive Biomarkers Detected by Comprehensive Genomic Profiling in Pineal Parenchymal Tumors (USCAP 2023)
    Clinically advanced PPTs appear to be genomically stable neoplasms with low GA per tumor, extremely limited targeted therapy options with the exception of the MTOR pathway and limited immunotherapy options given the absence of MSI-high status and low TMB.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    PD-L1 expression • MSI-H/dMMR • TMB-L • PD-L1 amplification
    |
    PD-L1 IHC 22C3 pharmDx
    over1year
    Molecular and Clinicopathologic Characterization of HER2-Overexpressed and HER2/neu-Amplified Squamous Cell Carcinoma of the Cervix (USCAP 2023)
    HER2 immunohistochemistry is a reliable predictive marker of HER2 gene amplification in squamous cell carcinoma of the cervix. HER2 overexpression and/or HER2 amplification are associated with poor prognostic factors, such as increased tumor grade, size, and depth of invasion, as well as nodal metastasis.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • JAK2 (Janus kinase 2) • BIRC3 (Baculoviral IAP repeat containing 3)
    |
    HER-2 overexpression • HER-2 amplification • PIK3CA mutation • PD-L1 amplification
    over1year
    PD-1-CD28 fusion protein strengthens mesothelin-specific TRuC T cells in preclinical solid tumor models. (PubMed, Cell Oncol (Dordr))
    Together, these results demonstrate the therapeutic potential of PD-1-CD28 co-expression in TRuC T cells to prevent PD-L1-induced T cell hypofunction.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • MSLN (Mesothelin) • CD28 (CD28 Molecule)
    |
    PD-1 expression • PD-L1 amplification
    over1year
    A cell-laden hydrogel as prophylactic vaccine and anti-PD-L1 amplifier against autologous tumors. (PubMed, J Control Release)
    Thus, without the need for precisely delivering immunoactivatory agents to tumor or locally remodeling tumor microenvironment, "priming" intractable or inaccessible tumors for subsequent ICB therapy could be achieved by prophylactic vaccination with (ACCO+CpG)@Gel. These findings highlighted (ACCO+CpG)@Gel as a generalized framework of protective vaccine strategy that could be broadly applicable to potentiate ICB therapy against multiple types of orthotopic tumors growing in different regions.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8)
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    PD-L1 expression • PD-L1 amplification
    over1year
    Genomic Profiling Reveals Differences in Primary Central Nervous System Lymphoma and Large B-Cell Lymphoma, With Subtyping Suggesting Sensitivity to BTK Inhibition. (PubMed, Oncologist)
    CGP of PCLs reveals biomarkers, genomic alterations, and molecular classifications predictive of BTKi efficacy and potential ICPI efficacy. Given the limitations of standard of care for PCL, CGP is critical to identify potential therapeutic approaches for patients in this rare form of lymphoma.
    Journal • Tumor Mutational Burden
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • ETV6 (ETS Variant Transcription Factor 6) • CREBBP (CREB binding protein) • PIM1 (Pim-1 Proto-Oncogene) • PRDM1 (PR/SET Domain 1)
    |
    PD-L1 amplification
    |
    FoundationOne® Heme CDx
    over1year
    Frequent Alterations of Driver Genes in Chromosome X and Their Clinical Relevance in Extranodal NK/T-Cell Lymphoma (ASH 2022)
    In addition, we proposed a novel molecular classification with biological and clinical relevance. Our findings can help improve diagnostic and therapeutic strategies in ENKTCL.
    Clinical • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ARID1A (AT-rich interaction domain 1A) • BCOR (BCL6 Corepressor) • KDM6A (Lysine Demethylase 6A) • JAK3 (Janus Kinase 3) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • CD27 (CD27 Molecule) • HLA-B (Major Histocompatibility Complex, Class I, B) • ITGAM (Integrin, alpha M) • CD58 (CD58 Molecule) • POT1 (Protection of telomeres 1) • DDX3X (DEAD-Box Helicase 3 X-Linked) • HLA-C (Major Histocompatibility Complex, Class I, C)
    |
    ARID1A mutation • CDKN2A deletion • PD-L1 amplification
    over1year
    Biomarker Analysis of Zanubrutinib and Tislelizumab Combination Therapy in Patients with Relapsed/Refractory B-Cell Malignancies (ASH 2022)
    Patients with PD-L1 gene amplification, PD-L1+ tumor cells, and high mRNA levels of CD3D, HLA-DRA, and LAG3 in baseline tumor tissue may be more responsive to zanubrutinib and tislelizumab combination therapy. A high mRNA level of REL or mutations in TP53 may contribute to resistance of zanubrutinib and tislelizumab combination therapy. Due to the limited number of samples, results must be interpreted with caution.
    Combination therapy • Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • HLA-DRA (Major Histocompatibility Complex, Class II, DR Alpha) • CD3D (CD3d Molecule) • REL (REL Proto-Oncogene)
    |
    PD-L1 expression • TP53 mutation • CD8 expression • PD-L1 amplification
    |
    VENTANA PD-L1 (SP263) Assay • HTG EdgeSeq DLBCL Cell of Origin Assay • Ventana CONFIRM anti-CD8 (SP57) Rabbit Monoclonal Primary Antibody
    |
    Tevimbra (tislelizumab) • Brukinsa (zanubrutinib)
    over1year
    Clinical Implementation of Pan-Cancer Mutational Signature Analysis and Landscape across 13,000 Solid Tumors (AMP 2022)
    Rule performance was orthogonally validated using MMR protein IHC or MSI status (MMR signature) across 431 cases or known clinical or molecular characteristics associated with each signature (smoking history, sun-exposed anatomic location, HPV-positivity, known POLE hotspot mutation, history of temozolomide) across 893 cases... Mutational signatures beyond MMR deficiency can be detected during routine clinical interpretation of NGS results from targeted, tumor-only sequencing. In this setting, signature analysis can contextualize tumor mutational burden, inform diagnosis, and shed light on tumor biology related to common mutagenic processes.
    Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker • Pan tumor
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • B2M (Beta-2-microglobulin)
    |
    POLE mutation • PD-L1 amplification
    |
    temozolomide
    over1year
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Not yet recruiting, German Cancer Research Center | Initiation date: Jul 2022 --> Dec 2022
    Trial initiation date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TROP2 (Trophoblast Cell Surface Antigen 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    over1year
    The Molecular Predictive and Prognostic Biomarkers in Metastatic Breast Cancer: The Contribution of Molecular Profiling. (PubMed, Cancers (Basel))
    These biomarkers will be classed according the level of evidence and, if possible, the ESCAT (ESMO) classification. Finally, we will provide some perspective on development in clinical practice for the main biomarkers.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    HER-2 amplification • PTEN mutation • NF1 mutation • PD-L1 amplification
    over1year
    Metastatic Gastric Adenocarcinoma in 23-Year-Old Female (ACG 2022)
    Improvements in micro-array-based gene expression profiling can help us to better delineate the tumor behavior and help us with treatment. Figure: Figure 1: a. CT abdomen - partially calcified gastric mass; b. EGD - A large infiltrative and ulcerated, noncircumferential mass on the lesser curvature of the gastric body; c. & d. Histopathology - H&E stain (20 x): gastric mucosa infiltrated by carcinoma cells with a signet-ring morphology.
    PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDH1 (Cadherin 1)
    |
    PD-L1 expression • HER-2 expression • MYC amplification • PD-L1 amplification • CDH1 expression • PD-L1 expression + HER-2 overexpression