Immune-checkpoint blockade (ICB) has been routinely implemented to treat bladder cancer; however, most patients have little or no clinical benefit. In this study, 348 pretreated metastatic urothelial cancer samples from the IMvigor210 cohort were used to identify important genes significantly associated with CD8+ T effector and immune checkpoint signatures. The immune checkpoint inhibitor score (IMS) scoring system was constructed to predict the immunotherapy responsiveness. Transcriptome analysis confirmed that the high IMS score group had significant immune activation with better prognosis and higher immunotherapy responsiveness, which was a powerful biomarker for predicting the prognosis and responsiveness of ICB. Tumor immune dysfunction and exclusion (TIDE) scores were calculated using 2031 external bladder cancer samples for further validation. We selected the important Hub genes as potential therapeutic targets, and validated the genes using genomic, transcriptomic, immunomic, and other multi-omics methods. In addition, we construct a risk prediction model which could stratify patients with bladder cancer and predict patient prognosis and ICB treatment responsiveness. In conclusion, this study identified effective biomarkers for the prediction of immune checkpoint inhibitor treatment responsiveness in bladder cancer patients and provided new immunotherapeutic targets.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-02019-6DOI Listing

Publication Analysis

Top Keywords

bladder cancer
20
immune checkpoint
16
effector immune
8
checkpoint signatures
8
prognosis responsiveness
8
cancer patients
8
cancer samples
8
checkpoint inhibitor
8
immunotherapy responsiveness
8
treatment responsiveness
8

Similar Publications

Long-term use of low-dose aspirin has been demonstrated to reduce cancer risk, but the duration of necessary medication use remains uncertain. This study aimed to investigate the long-term chemoprotective effect of aspirin among the Chinese population. This population-based study included all aspirin users between 2000 and 2019.

View Article and Find Full Text PDF

Objectives: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database.

Patients And Methods: This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC.

View Article and Find Full Text PDF

SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhanced anti-tumor activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase.

Lipids Health Dis

January 2025

Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, China.

Background: Bladder cancer is one of the most common malignancies of the urinary system. Despite significant advances in diagnosis and treatment, the compromised therapeutic effect of chemotherapeutic agents, such as Oxaliplatin (OXA), remains a major clinical challenge. Thus, a combination therapy is required to enhance the OXA's therapeutic effectiveness and improve patient outcomes.

View Article and Find Full Text PDF

Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma's potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate the biological effects of PAS on bladder cancer cell lines in vitro, as well as the combination with mitomycin C (MMC), using clinically relevant settings.

View Article and Find Full Text PDF

Clinical translation of the interconnected role of the microbiome and diet in genitourinary malignancies.

Urol Oncol

January 2025

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

A complex and often under-appreciated relationship exists between the human microbiome, diet, and the development or progression of cancer. There is likewise an emerging appreciation for the role that the human-associated microbiota play in mediating cancer treatment response. This seminar series covers our current understanding of the interplay between the microbiome and cancer in genitourinary malignancies inclusive of bladder, kidney, and prostate cancers.

View Article and Find Full Text PDF

Want 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!