Abstract
Urothelial bladder cancer (UBC) is one of the most prevalent and aggressive malignancies. Recent evidence indicates that the tumor microenvironment (TME), including a variety of immune cells, is a critical modulator of tumor initiation, progression, evolution, and treatment resistance. Mast cells (MCs) in UBC are possibly involved in tumor angiogenesis, tissue remodeling, and immunomodulation. Moreover, tumor-infiltration by MCs has been reported in early-stage UBC patients. This infiltration is linked with a favorable or unfavorable prognosis depending on the tumor type and location. Despite the discrepancy of MC function in tumor progression, MCs can modify the TME to regulate the immunity and infiltration of tumors by producing an array of mediators. Nonetheless, the precise role of MCs in UBC tumor progression and evolution remains unknown. Thus, this review discusses some critical roles of MCs in UBC. Patients with UBC are treated at both early and late stages by immunotherapeutic methods, including intravenous bacillus Calmette–Guérin instillation and immune checkpoint blockade. An understanding of the patient response and resistance mechanisms in UBC is required to unlock the complete potential of immunotherapy. Since MCs are pivotal to understand the underlying processes and predictors of therapeutic responses in UBC, our review also focuses on possible immunotherapeutic treatments that involve MCs.
Highlights
Urothelial bladder cancer (UBC) is a common disease with high morbidity and mortality rates, accounting for around 2.1% of all deaths due to cancer per year [1,2,3,4,5,6,7]
About 70% of patients with UBC present with disease confined to the mucosa or submucosa, which has a good prognosis [1,2,3,4,7,8,9,10,11,12,13]
NMIBC includes a diverse spectrum of diseases with a wide range of progression and recurrence rates that depend on several clinical and pathologic factors; the key to improving the prognosis of NMIBC is to reduce the risk of recurrence and progression [3,4,7,9,11]
Summary
Urothelial bladder cancer (UBC) is a common disease with high morbidity and mortality rates, accounting for around 2.1% of all deaths due to cancer per year [1,2,3,4,5,6,7]. Different options exist upon failure of first-line treatment, i.e., following failure of intravesical chemotherapy or BCG, and are largely dependent on the response to prior therapy [4,9,11,12]. Treatment with either antibody drug conjugates (ADCs), such as enfortumab-vedotin (EV), targets the adhesion molecule Nectin-4, or fibroblast growth factor receptor (FGFR) inhibitors, such as Erdafitinib, in patients harboring susceptible FGFR3 gene mutations (R248Cs, S249C, G370C, Y373C) or FGFR2/3 gene fusions (FGFR3-TACC3, FGFR3 BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7), and whose disease has progressed during or following platinum-based chemotherapy, with prior immunotherapy being allowed [2,4,9,14]. We present the clinical applications associated with therapeutically manipulating MCs as immunogens to overcome resistance against conventional immunotherapeutic drugs
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