Interleukin-17-positive mast cells influence outcomes from BCG for patients with CIS: Data from a comprehensive characterisation of the immune microenvironment of urothelial bladder cancer

Dowell, Alexander C.; Cobby, Ellen; Kong, Wen; Devall, Adam J.; During, Vinnie; Anderson, Jane; James, Nicholas D.; Cheng, Kar Keung; Bryan, Richard T.; Taylor, Graham S.

doi:10.1371/journal.pone.0184841

Cited by 23 publications

(32 citation statements)

References 57 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As well as detecting a diverse infiltrate of innate and adaptive immune cells including the above mentioned cell types, another study reported a significant role for IL-17 positive mast cells in influencing the outcomes from BCG therapy (20). Patients with carcinoma in situ (CIS, high grade cancer cells that are only in the innermost layer of the bladder lining) with higher numbers of IL-17+ mast cells showed significantly longer event-free survival after intravesical BCG therapy than patients with less IL-17+ mast cells.…”

Section: The Gold Standard Immunomodulatory Approach To Treat Nmibc: mentioning

confidence: 99%

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

2020

View full text Add to dashboard Cite

It is now well-recognized that the tumor microenvironment (TME) is not only a key regulator of cancer progression but also plays a crucial role in cancer treatment responses. Recently, several high-profile publications have demonstrated the importance of particular immune parameters and cell types that dictate responsiveness to immunotherapies. With this increased understanding of TME-mediated therapy, approaches that increase therapeutic efficacy by remodeling the TME are actively being pursued. A classic example of this, in practice by urologists for over 40 years, is the manipulation of the bladder microenvironment for the treatment of non-muscle invasive bladder cancer (NMIBC) by instillation of intravesical bacillus Calmette-Guerin (BCG). The success of BCG treatment is thought to be due to its ability to induce a massive influx of Th1-polarized inflammatory cells, production of Th1 inflammatory cytokines and the generation of tumor-targeted Th1-mediated cytotoxic responses. Whilst BCG immunotherapy is currently the best treatment for NMIBC, ∼30% of patients show no response to this treatment. Here we present a review highlighting a variety of promising alternative immunotherapies being developed that remodel the bladder tumor microenvironment. These include (1) the use of oncolytic viruses which selectively replicate within cancer cells whilst also modifying the immunological components of the TME, (2) manipulation of the bladder microbiome to augment the response to BCG or other immunotherapies (3) utilizing Toll-like Receptor agonists as anti-tumor agents due to their potent stimulation of innate and adaptive immunity and (4) the growing recognition that immunotherapeutic strategies that will have the largest impact on patients may require multiple therapeutic approaches combined together. The accumulating knowledge on TME remodeling holds promise for providing an alternative therapy for patients with BCG-unresponsive NMIBC.

show abstract

Section: The Gold Standard Immunomodulatory Approach To Treat Nmibc: mentioning

confidence: 99%

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

2020

View full text Add to dashboard Cite

show abstract

“…Mast cells negative correlated with several types of immune cells, such as macrophages M1/T cells CD8/T cells CD4 memory activated/T cells follicular helper, etc. the result consists with its pro-tumorigenic role in BLCA [31].…”

Section: Discussionmentioning

confidence: 99%

“…Mast cells infiltration has been showed involved in several types of cancer physiological and pathological conditions [30]. Previous studied showed that mast cells influence BLCA patient outcomes [31,32]. Mast cells could enhance bladder cancer metastasis by increasing CCL2/CCR2/EMT/MMP9 signals axis.…”

Section: Discussionmentioning

confidence: 99%

Immune Cell Infiltration in Bladder Cancer

Liu

et al. 2019

Preprint

View full text Add to dashboard Cite

Background Bladder cancer is one of the most common malignant diseases with high recurrence rates worldwide. Although immunotherapy has been applied in bladder cancer for a long period of time, the tumor-infiltrating immune cells (TIICs) in bladder cancer has not been systematical investigated. Methods CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs), was applied to calculate the TIICs fraction proportion in normal bladder tissues and in bladder cancer tissues with the TCGA data. Results compared to normal bladder tissue, B cells naïve, T cells CD4 memory resting and Mast cells resting fractions proportion decreased, and NK resting, macrophages M0 and macrophages M1 increased. In BLCAs tissue, pro-tumorigenic related immune cells were negatively correlated with anti-tumor immune cells. New tumor with locoregional had high fraction proportion of macrophages M0 and macrophages M1. Dendritic cells activated, Monocytes, macrophages M1, Tregs and T cells follicular helper significantly increased in low grade BLCAs. Tregs had a high proportion in BLCAs patients accepted low radiation dose. Conclusions This study indicates that macrophages M2 and Tregs could be the promising immunotherapy targets combined radiotherapy in BLCAs. The result provides valuable information to understand the immunity status in BLCAs.

show abstract

“…Other investigators have analyzed the immunebiology of CIS. Dowell et al analyzed the effect of Interleukin (IL)-17 positive mast cells on CIS [30]. The investigators observed an increased number of these cells in the CIS environment compared to other types of non-CIS NMIBC.…”

Section: Molecular Biology Of Cismentioning

confidence: 99%

CIS of the Bladder: Significance and Implications for Therapy

Mirabal

Taylor

Lerner

2019

BLC

View full text Add to dashboard Cite

Purpose of the review: To review the most recent literature with regards to the pathogenesis, diagnostics, clinical implications and treatment strategies for Carcinoma in Situ (CIS) of the Bladder. Recent findings: There have been advancements in understanding the genetic composition and biochemical behavior of CIS. Technological advancements including Photodynamic Diagnosis (PDD) with Hexaminolevulinate (HVA) better detect CIS compared to traditional white light (WL) cystoscopy. Recently published single and multi-center studies have enabled better understanding of the impact of CIS on clinical and cancer related outcomes, including disease recurrence and patient survival. Alternative intravesical chemotherapeutic and immunotherapies for CIS have been investigated, especially in the setting of Bacillus Calmette-Guerin (BCG) unresponsive disease. While these demonstrate a great deal of promise, they have not garnered much success. Summary: The genetics of CIS is linked to aggressive, and at times resistant disease, with increased cancer progression and associated clinically worse cancer specific outcomes. New technologies have enabled a more effective diagnosis of CIS. The development of a standardized definition for clinical trials and greater disease understanding will enable us to develop better treatment options.

show abstract

Interleukin-17-positive mast cells influence outcomes from BCG for patients with CIS: Data from a comprehensive characterisation of the immune microenvironment of urothelial bladder cancer

Cited by 23 publications

References 57 publications

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

Immune Cell Infiltration in Bladder Cancer

CIS of the Bladder: Significance and Implications for Therapy

Contact Info

Product

Resources

About