CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer

Yuan

J Cellular Molecular Medi

et al. 2019

The precision evaluation of prognosis is crucial for clinical treatment decision of bladder cancer (BCa). Therefore, establishing an effective prognostic model for BCa has significant clinical implications. We performed WGCNA and DEG screening to initially identify the candidate genes. The candidate genes were applied to construct a LASSO Cox regression analysis model. The effectiveness and accuracy of the prognostic model were tested by internal/external validation and pan-cancer validation and time-dependent ROC. Additionally, a nomogram based on the parameter selected from univariate and multivariate cox regression analysis was constructed.Eight genes were eventually screened out as progression-related differentially expressed candidates in BCa. LASSO Cox regression analysis identified 3 genes to build up the outcome model in E-MTAB-4321 and the outcome model had good performance in predicting patient progress free survival of BCa patients in discovery and test set. Subsequently, another three datasets also have a good predictive value for BCa patients' OS and DFS. Time-dependent ROC indicated an ideal predictive accuracy of the outcome model. Meanwhile, the nomogram showed a good performance and clinical utility. In addition, the prognostic model also exhibits good performance in pan-cancer patients. Our outcome model was the first prognosis model for human bladder cancer progression prediction via integrative bioinformatics analysis, which may aid in clinical decision-making. K E Y W O R D S bladder cancer, Gene Expression Omnibus (GEO), LASSO, prognosis, WGCNA S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Xiong Y, Yuan L, Xiong J, et al. An outcome model for human bladder cancer: A comprehensive study based on weighted gene co-expression network analysis.

Section: Introductionmentioning

confidence: 99%

An outcome model for human bladder cancer: A comprehensive study based on weighted gene co‐expression network analysis

Yuan

J Cellular Molecular Medi

et al. 2019

“…CD47-targeted NIR-PIT increases direct cancer cell death and phagocytosis, resulting in inhibited tumor growth and improved survival in a model of human bladder cancer [139]. A novel CD47-targeting fusion protein, termed SIRPαD1-Fc, was generated and found to increase the phagocytic and cytotoxic activities of macrophages against non-small cell lung cancer (NSCLC) cells [140]. Targeting both CD47 and autophagy in NSCLC xenograft models elicited enhanced anti-tumor effects, with the recruitment of macrophages, activated caspase-3, and overproduction of ROS at the tumor site [140,141].…”

Section: Dcs In Combination Tumor Immunotherapymentioning

confidence: 99%

“…A novel CD47-targeting fusion protein, termed SIRPαD1-Fc, was generated and found to increase the phagocytic and cytotoxic activities of macrophages against non-small cell lung cancer (NSCLC) cells [140]. Targeting both CD47 and autophagy in NSCLC xenograft models elicited enhanced anti-tumor effects, with the recruitment of macrophages, activated caspase-3, and overproduction of ROS at the tumor site [140,141]. DCs and cancer cells express PDL1 on their cell surface, which represses T cell activation [142].…”

Section: Dcs In Combination Tumor Immunotherapymentioning

confidence: 99%

Dendritic cell biology and its role in tumor immunotherapy

et al. 2020

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4 + and CD8 + T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DCbased tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.

Molecular Therapy - Oncolytics

“…Also, after NIR-PIT therapy for 5 consecutive weeks, statistical significance was reached in inhibition of tumor growth compared to repeated anti-CD47 immunotherapy. 86 …”

Section: Main Textmentioning

confidence: 99%

Endoscopic Molecular Imaging plus Photoimmunotherapy: A New Strategy for Monitoring and Treatment of Bladder Cancer

Yang

Liu

Yang

2020

Due to the high recurrence and progression rate of non-muscle invasive bladder cancer after transurethral resection of bladder tumor, some new optical imaging technologies have arisen as auxiliary imaging modes for white light cystoscopy to improve the detection rate of small or occult tumor lesions, such as photodynamic diagnosis, narrow-band imaging, and molecular imaging. White light cystoscopy is inadequate and imperfect for bladder cancer detection, and thus residual tumors or coexisting flat malignant lesions, especially carcinoma in situ , would be ignored during conventional resection. The bladder, a hollow organ with high compliance, provides an ideal closed operation darkroom for endoscopic molecular imaging free from interference of external light sources. Also, intravesical instillation of a molecular fluorescent tracer is simple and convenient before surgery through the urethra. Molecular fluorescent tracer has high sensitivity and specificity to tumor cells, and its mediated molecular imaging allows small or occult tumor lesion detection while minimizing false-positive results. Meanwhile, endoscopic molecular imaging provides a real-time and dynamic image during surgery, which helps urologists to perform high-quality and complete tumor resection through accurate judgment of tumor boundaries and depth of invasion. Photoimmunotherapy is a novel molecular targeted therapeutic pattern of photodynamic therapy that kills malignant cells selectively and minimizes the cytotoxicity to normal tissues. The combination of endoscopic molecular imaging and photoimmunotherapy used in initial treatment may avoid the need of repeat transurethral resection in strictly selected patients and improve oncological outcomes such as recurrence-free survival and overall survival after operation.