A5081609371- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Prostate Cancer Treatment and Research
- Radiopharmaceutical Chemistry and Applications
- Ferroptosis and cancer prognosis
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Lymphoma Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Renal cell carcinoma treatment
- Angiogenesis and VEGF in Cancer
- Cancer Diagnosis and Treatment
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Prostate Cancer Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Hedgehog Signaling Pathway Studies
- Inflammatory Biomarkers in Disease Prognosis
South Texas Accelerated Research Therapeutics
2013
Tennessee Oncology
2013
Sarah Cannon
2013
Novartis (United States)
2008
Pacific Southwest Research Station
2001
Significance Programmed death-ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating immune is regulated by distinct mechanisms has nonredundant roles in regulating anticancer immunity, PD-L1 both cell types important for predicting best response to atezolizumab non-small lung cancer.
Abstract Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis lead to durable clinical responses in subsets of cancer patients across multiple indications, including non-small cell lung (NSCLC), urothelial carcinoma (UC) and renal (RCC). Herein, we complement PD-L1 immunohistochemistry (IHC) tumor mutation burden (TMB) with RNA-seq 366 identify unifying indication-specific molecular profiles that can predict response blockade these types. Multiple machine learning approaches failed a...
CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading the hypothesis that their presence in tumors may predict response immunotherapy.Here, we test this combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled lung and bladder clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).ITGAE was identified as most significantly...
Atezolizumab [anti-programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, biomarkers of atezolizumab monotherapy for mCRPC.This phase Ia, open-label, dose-escalation dose-expansion (PCD4989g) enrolled patients with mCRPC who had progressed on sipuleucel-T or enzalutamide. was given intravenously every 3 weeks until...
Abstract Anti-angiogenic (AA) therapy is a cornerstone of metastatic clear cell renal carcinoma (ccRCC) treatment, but not everyone responds, and predictive biomarkers are lacking. CD31, marker vasculature, insufficient, the Angioscore, an RNA-based angiogenesis quantification method, costly, associated with delays, difficult to standardize, does account for tumor heterogeneity. Here, we developed interpretable deep learning (DL) model that predicts Angioscore directly from ubiquitous...
B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder characterized by the surface expression of CD20, CD5 antigens, as well receptor CD40. Activation CD40 its ligand (CD40L) induces proliferation and rescues cells from spontaneous chemotherapy-induced apoptosis. activation also secretion cytokines, such IL-6, IL-10, TNF-alpha, IL-8, GM-CSF, which are involved in tumor cell survival, migration, interaction with microenvironment. Here we demonstrate that primary B-CLL...
Abstract Programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death-1 (PD-1), are important negative regulators of immune activation. Therapeutically targeting PD-1/PD-L1 in diffuse large B-cell lymphoma (DLBCL) patients with a single agent has limited activity, meriting deeper understanding this complex biology available PD-L1 clinical assays. In study, we leveraged 2 de novo DLBCL phase 3 trials (GOYA MAIN) to better understand the biologic relevance DLBCL. was expressed on...
Abstract Background: Current treatments for mCRPC include the androgen receptor antagonist enzalutamide (enza). Enza may enhance IFNγ signaling and sensitize tumor cells to immune-mediated cell killing, making it a candidate combinations with PD-L1/PD-1 inhibitors. Responses have been observed in patients (pts) receiving inhibitor or without enza. Therefore, atezolizumab (atezo), humanized anti-PD-L1 monoclonal antibody that inhibits interaction between PD-L1 its receptors, is being examined...
12000 Background: PD-L1 expression has limitations as a biomarker for checkpoint immunotherapy (CI). Prior atezolizumab (atezo) monotherapy studies suggest improved efficacy in high tissue tumor mutational burden (tTMB-H) cohorts. We report large retrospective analysis associating tTMB with neoantigen load (NAL) and CI across multiple studies, types lines of therapy. Methods: Tissue TMB was evaluated by the FoundationOne (F1) assay 7 atezo studies: NSCLC n= 342 (FIR, BIRCH, POPLAR, OAK),...
Abstract Purpose: Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety efficacy of atezolizumab (anti–PD-L1) + radium-223 dichloride (radium-223) in men mCRPC. Patients Methods: This phase Ib study evaluated mCRPC bone lymph node and/or visceral metastases that progressed androgen pathway inhibitor treatment. Following assessment concurrent dosing, 45 were...
Abstract Anchored reference loci provide a framework for comparative mapping. They are landmarks to denote conserved chromosomal segments, allowing the synthesis of genetic maps from multiple sources. We evaluated 90 expressed sequence tag polymorphisms (ESTPs) loblolly pine (Pinus taeda L.) this function. Primer sets were assayed amplification and polymorphism in six pedigrees, representing two subgenera Pinus distant member Pinaceae, Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco). On...
The application of modeling and simulation techniques is increasingly common in the preclinical stages drug development process. GDC-0917 [(<i>S</i>)-1-((<i>S</i>)-2-cyclohexyl-2-((<i>S</i>)-2-(methylamino)propanamido)acetyl)-<i>N</i>-(2-(oxazol-2-yl)-4-phenylthiazol-5-yl)pyrrolidine-2-carboxamide] a potent second-generation antagonist inhibitor apoptosis (IAP) proteins that being developed for treatment various cancers. has low to moderate clearance mouse (12.0 ml/min/kg), rat (27.0 dog...
104 Background: Biomarkers of clinical benefit immunotherapies, such as non-synonymous mutations, mutational load, PD-L1 IHC and immune signatures, have not been systematically evaluated in mUC patients (pts) treated with anti–PD-L1 agents. Methods: Exploratory analyses genetic predictors response to atezo were performed on archival tumor specimens from pts (NCT02108652 cohort 2). expression samples was assessed by (SP142 assay) associated determined RECIST v1.1 (central review). Gene...
409 Background: IMvigor211 is a global study of atezo vs chemo in platinum-treated mUC. The did not meet its primary endpoint overall survival (OS) programmed death-ligand 1 (PD-L1)–selected patients (pts), but exploratory analyses showed improved OS for the intent-to-treat (ITT) population. Here we compare clinical outcomes ITT and prespecified PD-L1 subgroups with those defined by immune transcriptional gene expression (tGE) signatures TMB. Methods: Pts ≤ 2 prior lines therapy mUC who...
5011 Background: Tumor mutational burden (TMB), PD-L1 expression, T-effector gene expression (GE) and a fibroblast TGF-β–response signature (F-TBRS) are associated with clinical outcomes atezo mono in mUC (Mariathasan, Nature, 2018). Here we explore the potential predictive role of these biomarkers APOBEC mutagenesis IMvigor130. Methods: Pts receiving first-line (1L) treatment (tx) were randomized 1:1:1 to + PBC, mono, or placebo PBC. Coprimary efficacy endpoints PFS OS. Planned exploratory...
Abstract Immunogenetic variation in humans is important research, clinical diagnosis and increasingly a target for therapeutic intervention. Two highly polymorphic loci play critical roles, namely the human leukocyte antigen (HLA) system, which version of major histocompatibility complex (MHC), Killer-cell immunoglobulin-like receptors (KIR) that are relevant responses natural killer (NK) some subsets T cells. Their accurate classification has typically required use dedicated biological...
It is estimated that the
187 Background: In the past decade, several therapies have been approved for mCRPC. However, most pts develop resistance and experience disease progression. Thus, there remains a high unmet need. Atezo (anti–PD-L1) blocks interaction between PD-L1 its receptors, PD-1 B7.1, thereby restoring anti-tumor immunity. has demonstrated clinical efficacy in many tumor types. Here we report safety activity of atezo with mCRPC from Phase Ia study (PCD4989g; NCT01375842). Methods: Eligible previously...
Meeting abstracts Atezolizumab (anti-PD-L1) has demonstrated robust clinical activity in UBC [[1][1]]. Elevated PD-L1 expression on tumor-infiltrating immune cells (IC) is associated with increased efficacy; however, the contribution of other biomarkers unknown. In this study, we