Immune escape mechanisms and immunotherapy of urothelial bladder cancer DOI Open Access
Zhao Yang, Yinyan Xu, Ying Bi

et al.

Journal of Clinical and Translational Research, Journal Year: 2021, Volume and Issue: unknown

Published: Jan. 1, 2021

Urothelial bladder cancer (UBC) is a common malignant tumor of the urogenital system with high rate recurrence. Due to sophisticated and largely unexplored mechanisms tumorigenesis UBC, classical therapeutic approaches including transurethral resection radical cystectomy combined chemotherapy have remained unchanged for decades. However, increasingly in-depth understanding microenvironment composition tumor-infiltrating lymphocytes novel immunotherapeutic strategies been developed. Bacillus Calmette-Guerin (BCG) therapy, immune checkpoint blockades, adoptive T cell immunotherapy, dendritic (DC) vaccines, etc., all intensively investigated as immunotherapies UBC. This review will discuss recent progress in escape immunotherapy UBC.Based on comprehensive search PubMed ClinicalTrials.gov database, this included literature reporting UBC clinical trials assessing effect or cells patients published English between 1999 2020.Immune surveillance, balance, are three major processes that occur during tumorigenesis. First, role immunosuppressive cells, molecules, signaling DCs introduced elaborately section. In addition, BCG, inhibitors, cytokines, DCs, macrophages summarized detail. Finally, need explore mechanisms, molecular characteristics landscape development robust also proposed discussed.At present, BCG blockades approved by US Food Drug Administration treatment achieved encouraging results, expanding traditional surgery-based UBC.Immunotherapy has desirable results which not only improve overall survival but reduce recurrence occurrence treatment-related adverse events patients. indicators predict effectiveness therapy strategies, such combination regimen inhibitor chemotherapy, should be further studied.

Language: Английский

Mechanisms of BCG immunotherapy and its outlook for bladder cancer DOI
C. Pettenati, Molly A. Ingersoll

Nature Reviews Urology, Journal Year: 2018, Volume and Issue: 15(10), P. 615 - 625

Published: July 10, 2018

Language: Английский

Citations

391
An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer DOI Creative Commons
Sia V. Lindskrog, Frederik Prip, Philippe Lamy

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 16, 2021

Abstract The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed NMIBC ( n = 834). Transcriptomic identifies four classes (1, 2a, 2b and 3) reflecting tumor biology disease aggressiveness. Both transcriptome-based subtyping the level chromosomal instability provide independent prognostic value beyond established clinicopathological parameters. High instability, p53-pathway disruption APOBEC-related mutations are significantly associated transcriptomic class 2a poor outcome. RNA-derived immune cell infiltration chromosomally unstable tumors enriched 2b. Spatial proteomics confirms higher demonstrates association between lower recurrence rates. Finally, documented 1228 validation samples using a single sample classification tool. classifier provides framework for biomarker discovery optimizing treatment surveillance next-generation trials.

Language: Английский

Citations

263
Adaptive Immune Resistance to Intravesical BCG in Non–Muscle Invasive Bladder Cancer: Implications for Prospective BCG-Unresponsive Trials DOI Open Access
Max Kates, Andrés Matoso, Woonyoung Choi

et al.

Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 26(4), P. 882 - 891

Published: Nov. 11, 2019

To characterize immune cell expression among patients with non-muscle invasive bladder cancer (NMIBC) treated Bacillus Calmette-Guerin (BCG).Patients NMIBC intravesical BCG (2008-2015) were identified, and a tissue microarray was constructed using paired pre- post-BCG samples. Among undergoing BCG, cystoscopic evaluation began 3 months after initiating treatment to determine therapeutic response. IHC performed for CD8, CD4, FoxP3, PD-L1 (SP-142 22C3), PD-1. A full slide review of PD-L1+ staining tumors CD8 colocalization. RNA-seq on cored from available specimens. We compared populations between responders nonresponders, pretreatment postreatment tumor Baseline in the naïve population then validated separate cohort.The final cohort contained 63 cases, including 31 32 nonresponders. No differences or FoxP3 identified (22C3 SP-142) observed 25% 28% nonresponders 0% 4% (P < 0.01). cells colocalized CD8+ T cells. In addition, therapy did not increase gene (RNA-seq) protein levels (IHC). The number CD4+ very low (12%) high PD-L1- (50%, P 57 baseline (22C3) similar (26%).One mechanism failure may be adaptive resistance. predicts an unfavorable response if validated, could used guide decisions.

Language: Английский

Citations

129
T1 bladder cancer: current considerations for diagnosis and management DOI
Brian J. Jordan, Joshua J. Meeks

Nature Reviews Urology, Journal Year: 2018, Volume and Issue: 16(1), P. 23 - 34

Published: Oct. 15, 2018

Language: Английский

Citations

127
Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches DOI Creative Commons
Dongkui Song, Thomas Powles, Lei Shi

et al.

The Journal of Pathology, Journal Year: 2019, Volume and Issue: 249(2), P. 151 - 165

Published: May 18, 2019

Abstract With the mechanistic understanding of immune checkpoints and success in checkpoint blockade using antibodies for treatment certain cancers, immunotherapy has become one hottest areas cancer research, with promise long‐lasting therapeutic effect. Currently, however, only a proportion cancers have good response to inhibition immunotherapy. Better resistance mechanisms is essential fully explore potential cure majority cancers. Bladder cancer, most common aggressive malignant diseases, been successfully treated both at early advanced stages by different immunotherapeutic approaches, bacillus Calmette–Guérin (BCG) intravesical instillation anti‐PD‐1/PD‐L1 blockade, respectively. Therefore, it provides model investigate improve efficiency Here, we review bladder equal weight on BCG therapies demonstrate why how can be used as study predictors shine light further development approaches predictive biomarkers other malignancies. We underlying predictors, including limits our knowledge. then highlight briefly adaptation developed therapy. Finally, new which may translated into human © 2019 The Authors. Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

Citations

84
Molecular profiling in muscle‐invasive bladder cancer: more than the sum of its parts DOI Open Access
Gottfrid Sjödahl, Chelsea Jackson, John M.S. Bartlett

et al.

The Journal of Pathology, Journal Year: 2019, Volume and Issue: 247(5), P. 563 - 573

Published: Jan. 3, 2019

Bladder cancers are biologically and clinically heterogeneous. Recent large-scale transcriptomic profiling studies focusing on life-threatening muscle-invasive cases have demonstrated a small number of molecularly distinct clusters that largely explain their heterogeneity. Similar to breast cancer, these reflect intrinsic urothelial cell-type differentiation programs, including those with luminal basal cell characteristics. Also like each cell-based subtype demonstrates profile regard its prognosis expression therapeutic targets. Indeed, suggest subtype-specific differential responses cytotoxic chemotherapy therapies inhibit targets, growth factors (EGFR, ERBB2, FGFR) immune checkpoint (PD1, PDL1) inhibitors. Despite burgeoning evidence for important clinical implications, subtyping has yet enter into routine practice. Here we review the conceptual basis in bladder cancer discuss behind proposed uses as prognostic or predictive test. In deliberating barriers implementation, pitfalls associated illustrate simple immunohistochemistry (IHC)-based algorithm may serve faster, less expensive alternative. Envisioned research tool can easily be translated pathology workflow, IHC-based potential more rapidly establish utility (or lack thereof) type Copyright © 2019 Pathological Society Great Britain Ireland. Published by John Wiley & Sons, Ltd.

Language: Английский

Citations

81
Diagnosis and Staging of Bladder Cancer DOI
Hamed Ahmadi, Vinay Duddalwar, Siamak Daneshmand

et al.

Hematology/Oncology Clinics of North America, Journal Year: 2021, Volume and Issue: 35(3), P. 531 - 541

Published: April 16, 2021

Language: Английский

Citations

70
Non–muscle-invasive bladder cancer molecular subtypes predict differential response to intravesical Bacillus Calmette-Guérin DOI Open Access
Florus C. de Jong, Teemu D. Laajala, Robert F. Hoedemaeker

et al.

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(697)

Published: May 24, 2023

The recommended treatment for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) instillations. However, only 50% of benefit from this therapy. If progression to advanced disease occurs, then must undergo a radical cystectomy risks substantial morbidity and poor clinical outcome. Identifying tumors unlikely respond BCG can translate into alternative treatments, such as early cystectomy, targeted therapies, or immunotherapies. Here, we conducted molecular profiling 132 BCG-naive HR-NMIBC 44 recurrences after (34 matched), which uncovered three distinct response subtypes (BRS1, 2 BRS3). Patients BRS3 had reduced recurrence-free progression-free survival compared BRS1/2. expressed high epithelial-to-mesenchymal transition basal markers an immunosuppressive profile, was confirmed spatial proteomics. Tumors that recurred were enriched BRS3. BRS stratification validated in second cohort 151 HR-NMIBC, the outperformed guideline-recommended risk based on clinicopathological variables. For application, commercially approved assay able predict area under curve 0.87. These will allow improved identification at highest have potential be used select more appropriate treatments BCG.

Language: Английский

Citations

33
The Urinary Microbiome: Implications in Bladder Cancer Pathogenesis and Therapeutics DOI
Petar Bajic, Alan J. Wolfe, Gopal N. Gupta

et al.

Urology, Journal Year: 2019, Volume and Issue: 126, P. 10 - 15

Published: Jan. 4, 2019

Language: Английский

Citations

67
Sex Differences in Bladder Cancer Immunobiology and Outcomes: A Collaborative Review with Implications for Treatment DOI
Madhuri Koti,

Molly A. Ingersoll,

Shilpa Gupta

et al.

European Urology Oncology, Journal Year: 2020, Volume and Issue: 3(5), P. 622 - 630

Published: Sept. 20, 2020

Language: Английский

Citations

54