-
The most common malignant tumor of the urinary tract system is urothelial carcinoma (UC). With the introduction of novel immunologic therapy options in both metastatic and localized settings, the exploration of immunologic biomarkers to predict potential treatment success has become a focus of clinical translational research.
Published August 12, 2022
-
The algorithms for treatment of metastatic cancers are evolving due to positive results obtained with immunotherapy. Therapeutics approaches to stimulate the immune system have already been used in the treatment of kidney and bladder cancer, such as the administration of cytokines and BCG therapy, confirming the immunogenicity of these tumors.
Published February 2, 2017
-
CHICAGO, IL USA (UroToday.com) - Dr. Thomas Powles presented an exciting phase I clinical trial evaluating the safety and early efficacy data of MPDL3280A, a human anti-PD-L1 monoclonal antibody, in patients with treatment-refractory, metastatic urothelial carcinoma.
Published June 1, 2014
-
Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition.
Published November 27, 2020
-
Targeting PD-1/PD-L1 immune checkpoints is a new therapeutic tool in patients with locally advanced and metastatic clear cell renal cell carcinoma (CCRCC). The purpose of this review is to offer clinicians an updated translational insight into the current status of a therapeutic alternative that may impact significantly patient's life.
Published January 17, 2019
-
Background:
Renal cell carcinoma (RCC) is the most common type of renal malignancy with 87% frequency. As a global health problem, kidney cancer is responsible for 2.
Published January 22, 2020
-
Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites.
The genes of 28 types of immune cells were obtained from previous studies.
Published October 27, 2020
-
Immunohistochemical PD-L1 assessment is currently used to identify responders towards checkpoint inhibitors although it is limited by inter-observer effects. Here, we conducted a multi-center round robin test to prove the possibility of assessing the PD-L1 status by gene expression to avoid inter-observer effects.
Published April 3, 2018
-
Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients.
To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT).
Published February 1, 2023
-
Urothelial carcinoma remains a devastating disease with a poor prognosis. Though immune therapy with Bacillus Calmette-Guérin (BCG) has been used for localized bladder cancer for years, only immune-checkpoint blockade with antiprogrammed cell-death 1 (anti-PD-1) and antiprogrammed cell-death ligand 1 (anti-PD-L1) inhibitors have demonstrated improvement in survival of patients with metastatic disease.
Published February 14, 2019
-
The ability of tumor cells to avoid immune destruction (immune escape) as well as their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer.
Published February 16, 2016
-
Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown.
Published January 16, 2018
-
Patients with muscle-invasive urothelial bladder cancer post neoadjuvant cisplatin-based chemotherapy with pathologic advanced disease (ypT3, ypT4, ypN+) at radical cystectomy have a significantly worse five-year overall survival.
Published May 24, 2021
-
Introduction: The immune checkpoint inhibitors (ICI) programmed cell death protein and ligands 1 (PD1- and PD-L1) as well as cytotoxic T-lymphocyte-associated protein 4 have demonstrated clinical efficacy in genitourinary cancer.
Published May 18, 2020
-
Non-muscle invasive bladder cancer (NMIBC), which is characterized by a recurrence rate of approximately 30% and very long treatment times, remains a major unresolved problem for patients and the health care system.
Published October 20, 2020
-
Immune checkpoint inhibitors (ICI) are then backbone in the therapy of metastatic renal cell carcinoma (RCC). The aim of this analysis was to explore the different expression of the ICI PD-L1, BTLA, and TIM-3 at the different tumor locations of the invasion front and the tumor center.
Published January 23, 2024
-
We have previously reported that tumor antigen-specific DNA vaccination in mice led to an increase in IFNγ-secreting T cells and an increase in tumor expression of PD-L1. Further, we demonstrated that increasing the encoded antigen's MHC-binding affinity led to increased PD-1 expression on antigen-specific CD8(+) T cells.
Published August 3, 2016
-
Pathogenic mutations in homologous recombination (HR) DNA repair genes may be associated with increased tumor mutational burden and numbers of tumor-infiltrating lymphocytes (TIL). Though HR-deficient prostate tumors have been anecdotally associated with improved responses to immunotherapy, it is unclear whether HR mutations or HR deficiency (HRD) scores predict for increased T-cell densities in this cancer.
Published September 20, 2021
-
The response to immune checkpoint inhibitors (ICIs) or enfortumab vedotin is limited in patients with upper urinary tract urothelial carcinoma (UTUC), and the development of new targeted therapy for UTUC is eagerly needed.
Published March 7, 2024
-
Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses.
Published October 20, 2017
-
Metastatic urothelial carcinoma (UC) remains an aggressive disease associated with limited treatment options and a reduced survival. In spite of this, the first-line treatment based on platinum-based combinations has remained virtually unchanged for the last 20-30 years.
Published March 22, 2018
-
We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC).
In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks.
Published October 26, 2018
-
Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti-PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment.
Published October 31, 2019
-
Clear cell Renal cell carcinoma (ccRCC) is an immunogenic tumor. B7 family members, such as CTLA-4, PD-1, and PD-L1, are the main components of immune checkpoints that regulate various immune responses.
Published March 13, 2023
-
Penile squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options when the tumor is unresectable and/or chemorefractory. Triplet systemic chemotherapy regimens including taxane and cisplatin are recommended, but the response duration can be short and the treatment-related toxicity high.
Published December 13, 2017
-
After years of trials, Programmed Death Ligand and Receptor targeting finally debuts as a firstline therapy in combination and as a single agent regimen at the 2016 European Society of Medical Oncology (ESMO) Congress.
Published January 25, 2017
-
Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response.
Published January 31, 2018
-
Immunotherapy based on BCG vaccination is an effective treatment in bladder cancer, but a positive response is restricted to a subset of patients and for a limited period of time only. This suggests that T cells antitumor responses are effective but can become compromised in bladder cancer.
Published December 19, 2016
-
Bladder cancer is one of the most prevalent cancers worldwide. Unfortunately, there have been few advances in its clinical management due to a poor understanding of the correlations between its molecular and clinical features.
Published April 10, 2018
-
Despite a long history of immunotherapeutic approaches to treatment, most genitourinary malignancies are not cured by existing immunotherapy regimens. More recently, cell surface molecules known as immune checkpoints have become the focus of efforts to develop more effective immunotherapies.
Published March 9, 2016
-
BUB1 mitotic checkpoint serine/threonine kinase B encoded by BUB1B gene is a member of the spindle assembly checkpoint family. Several reports have demonstrated that overexpression of BUB1B is associated with cancer progression and prognosis.
Published February 17, 2021
-
A novel immune checkpoint, CD155/T-cell immunoreceptor with Ig and ITIM domains, has been recognized as a new therapeutic target in addition to conventional immune checkpoints, such as anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-L1), for urothelial carcinoma (UC).
Published October 28, 2022
-
Although immune checkpoint inhibitors (ICIs) are established as effective cancer therapies, overcoming therapeutic resistance remains a critical challenge. Here we identify interleukin 6 (IL-6) as a correlate of poor response to atezolizumab (anti-PD-L1) in large clinical trials of advanced kidney, breast, and bladder cancers.
Published January 6, 2023
-
To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC).
Published December 15, 2021
-
Predicting response to ICI therapy among patients with renal cell carcinoma (RCC) has been uniquely challenging. We analyzed patient characteristics and clinical correlates from a retrospective single-site cohort of advanced RCC patients receiving anti-PD-1/PD-L1 monotherapy (N = 97), as well as molecular parameters in a subset of patients, including multiplexed immunofluorescence (mIF), whole exome sequencing (WES), T cell receptor (TCR) sequencing, and RNA sequencing (RNA-seq).
Published April 9, 2021
-
To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC.
Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included.
Published September 7, 2019
-
Recently, immunotherapy based on blocking immune checkpoints with programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) antibodies has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), but the significance of their expression in the tumor microenvironment is unclear.
Published April 30, 2019
-
Recently, the association of immunological checkpoint marker programmed death ligand-1 (PD-L1) and the prognosis of various cancers has always been a research hotspot. The objective of this study is to assess the clinical value of PD-L1 as a novel prognostic biomarker of renal cell carcinoma (RCC).
Published December 11, 2015
-
Clear cell renal cell carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences the tumor immune microenvironment in ccRCC.
Published July 26, 2021
-
Genomic alterations (GA) in NF2 tumor-suppressor gene have been associated with aggressive behavior in kidney tumors. We used comprehensive genomic profiling (CGP) to evaluate the frequencies of NF2 GA in histologic subtypes of kidney tumors and co-occurring GA in other genes and biomarkers.
Published March 16, 2023
-
Previous studies noted discordance of programmed death-1 (PD-1) and one of its ligands (PD-L1) across patient-matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome.
Published January 14, 2020
-
Programmed Death-Ligand (PD-L1) expression has predictive value for response to immune-checkpoint inhibitor treatment in urothelial cancer patients. The consistency of PD-L1 expression amongst different specimen types is however unknown.
Published July 17, 2018
-
The regulation of immune responses occurring during Bacillus Calmette-Guerin (BCG) therapy need to be better scrutinized in order to identify new targetable pathways for non-muscle invasive bladder cancer treatment.
Published August 8, 2018
-
Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone.
Published January 9, 2024
-
In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) has led to the development of biologically-driven targeted therapies. Hypoxia-inducible factors (HIFs), angiogenic growth factors, von Hippel⁻Lindau (VHL) gene mutations, and oncogenic microRNAs (miRNAs) play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma.
Published December 12, 2018
-
Harnessing the host immune system to combat genitourinary cancers has key theoretical advantages over other anticancer strategies including specificity and memory which should translate to favorable tolerability and response durability in the clinic.
Published September 5, 2018
-
Since 2016, five new programmed cell death protein 1/ligand 1 (PD-1/L1) checkpoint inhibitors have been approved for metastatic urothelial carcinoma. This review will summarize the data supporting the widespread use of these agents and highlight areas of ongoing clinical development.
Published March 24, 2019
-
Renal cell carcinoma (RCC) was recognized as an immunologically sensitive cancer over 30 years ago. The first therapies to affect the course of RCC were cytokines (interferon alfa-2B and interleukin-2).
Published March 12, 2019
-
The expression status of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and the infiltration of CD8+ T cells in tumor tissues are considered to be related to immunotherapy efficacy and patient prognosis.
Published February 22, 2021
-
The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors.
Published November 3, 2015