The dynamic roles of the bladder tumour microenvironment

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment Research

Background:

• Bladder cancer research often overlooks the stromal compartment, despite its importance in disease progression and treatment response.
• The tumor microenvironment (TME) in bladder cancer, termed bladder TME (bTME), involves dynamic intercellular communication crucial for tumor evolution and metastasis.
• Novel concepts like the metastatic TME (met-TME) suggest distinct microenvironments supporting distant colonization.

Purpose of the Study:

• To highlight the understudied role of the bladder TME (bTME) and metastatic TME (met-TME) in bladder cancer.
• To emphasize the potential of targeting stromal components alongside tumor cells for improved therapeutic outcomes.
• To advocate for further investigation into these novel TME niches.

Main Methods:

• Review and synthesis of current research on bladder cancer, focusing on the tumor microenvironment.
• Analysis of the roles of collagens and discoidin domain receptors in cancer metastasis and therapy resistance.
• Conceptualization of the bladder TME (bTME) and metastatic TME (met-TME) as distinct niches.

Main Results:

• The stromal compartment and intercellular communications within the bTME significantly influence bladder tumor progression, metastasis, and response to therapies.
• Collagens and discoidin domain receptors are implicated in the metastatic cascade and resistance to immune checkpoint inhibitors.
• The stroma plays a divergent role in response to various treatments, including BCG immunotherapy, chemotherapy, and radiotherapy.

Conclusions:

• The bladder TME (bTME) and metastatic TME (met-TME) represent underexplored therapeutic targets in bladder cancer.
• Understanding these microenvironments is key to developing novel strategies that co-target tumor and stromal cells.
• Targeting these niches holds promise for improving outcomes in patients with advanced bladder cancer.