Tumor-Associated Mast Cells in Urothelial Bladder Cancer: Optimizing Immuno-Oncology

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.

Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial

“…In contrast to the literature that focuses on PD-L1 in cancer cells, a few studies have shown that the expression of PD-L1 on tumor-associated micro-conduit endothelial cells limit the infiltration and activity of Teff cells and enhance infiltration of Treg cells 28 by binding with PD-1 on T cells, which leads to the immune evacuation of tumor cells and a poor prognosis 29 . Therefore, some effort has been made in assuaging and even removing the barrier imposed by high PD-L1 expression on BECs to improve immune therapeutic efficacy.…”

JAM3: A prognostic biomarker for bladder cancer via epithelial–mesenchymal transition regulation

“…M2 macrophages promote tumor angiogenesis and tumor cell development, blocking the function of T cells, and are associated with poor prognosis, also in BC [ 51 , 52 ]. While, mast cells exert pro- or anti-tumor effects due to different tumors, including BC and different TMEs [ 53 , 54 ]. Meanwhile, a significant negative correlation with activated dendritic cells and CD8+ T cells was observed as well.…”

The Clinical Significance of Serum Free Light Chains in Bladder Cancer

“…Evidence of this may be the presence of free light chains found by other researchers in the areas of mast cell infiltration. On the other hand, the inhibition of FLCs and, as a result, mast cells appears to be a promising therapeutic target for the treatment of cancers [22][23][24][25][26].…”