Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti-PD-1 monotherapy and combination immunotherapy regimens.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718162 | PMC |
| http://dx.doi.org/10.1126/science.aar3593 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
LncRNA PGM5-AS1 Impairs the Resistance of Cervical Cancer to Cisplatin by Regulating the Hippo and PI3K-AKT Pathways.
Biochem Genet
December 2024
Department of Obstetrics and Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), No.216, Guanshan Avenue, Hongshan District, Wuhan, 430074, Hubei, China.
Cisplatin, a platinum-based chemotherapeutic agent, can be used to treat cervical cancer (CC), but cisplatin resistance is increased during the cisplatin treatment. Long non-coding RNA PGM5-AS1 reportedly participates in CC tumorigenesis; however, its role in CC patients with cisplatin resistance has not been revealed. The present aimed to examine the role of PGM5-AS1 in modulating cisplatin resistance in CC.
View Article and Find Full Text PDFInactivation of the SLC25A1 gene during embryogenesis induces a unique senescence program controlled by p53.
Cell Death Differ
December 2024
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA.
View Article and Find Full Text PDFA novel development of optimized hybrid MPPT controller for fuel cell systems with high voltage transformation ratio DC-DC converter.
Sci Rep
December 2024
Department of Electrical Engineering, College of Engineering, King Saud University, Riyadh, 11421, Saudi Arabia.
The world is moving towards the utilization of hydrogen vehicle technology because its advantages are uniformity in power production, more efficiency, and high durability when compared to fossil fuels. So, in this work, the Proton Exchange Membrane Fuel Stack (PEMFS) device is selected for producing the energy for the hydrogen vehicle. The merits of this fuel technology are the possibility of operating less source temperature, and more suitability for stationery and transportation applications.
View Article and Find Full Text PDFIron oxide nanoparticles induce ferroptosis under mild oxidative stress in vitro.
Sci Rep
December 2024
School of Medicine, Yichun University, Yichun, 336000, China.
Iron oxide nanoparticles (IONPs) have the potential to be utilized in a multitude of fields, including biomedicine. Consequently, the potential health risks associated with their use must be carefully considered. Most biosafety evaluations of IONPs have focused on examining the impact of the material's distinctive physicochemical attributes.
View Article and Find Full Text PDFEnhancing antibody levels and T cell activity of quadrivalent influenza vaccine by combining it with CpG HP021.
Sci Rep
December 2024
State Key Laboratory for Diagnosis, Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Influenza virus infections are a serious danger to people's health worldwide as they are responsible for seasonal flu outbreaks. There is an urgent need to improve the effectiveness and durability longevity of the immune response to influenza vaccines. We synthesized the CpG HP021 and examined the impact of it on the immune response to an influenza vaccine.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!