Editorial: Understanding The Bladder Tumor Microenvironment to Optimize

Mathieu Rouanne ^1* Derré Laurent ^2*

• ¹ Columbia University, New York City, United States
• ² Université de Lausanne, Lausanne, Vaud, Switzerland

Bladder cancer remains a public health concern due to its prevalence, high risk of recurrence and associated cost of management. While significant advances have been made in the treatment of bladder cancer over the last five years, including new standard of care in the first line treatment of metastatic bladder cancer with antibody drug conjugate and PD-1 blockade, maintenance PD-L1 blockade and FDA-approval of PD-1 blockade in the adjuvant setting after radical cystectomy for high-risk tumors, robust predictive biomarkers are still missing. Currently, a multitude of novel immunostimulatory drugs, such as bispecific T cell engagers, CAR-T cells, recombinant interleukins, oncolytic viruses are being tested in patients with bladder tumors. The clinical development of some novel immunomodulatory agents is rapidly evolving at earlier tumor stages in organconfined disease. Understanding the roles, functions and responses of immune and nonimmune cells in the bladder tumor microenvironment is critical to foster the successful development of immuno-modulatory drugs in non-metastatic bladder tumors.In this cutting-edge collection of review and original articles, our goal is to provide a discussion on the role and mechanisms of immune and non-immune components of the bladder tumor microenvironment, from the host's protective immunosurveillance to the response to immunotherapy. We wish to encourage discussion and cross-fertilization between scientists, and clinicians among the various roles and aspects of the bladder tumor microenvironment and its responses to immune modulation, to further our knowledge in this field. Anlotinib is a tyrosine kinase inhibitor with anti-angiogenic and fibroblast growth factor receptor (FGFR) inhibitory effects. Tislelizumab is a programmed death-1 (PD-1) immune checkpoint inhibitor. Although the tumor from both patients was programmed death ligand-1 (PD-L1)-negative and only one patient had FGFR3 mutation, both patients showed a partial remission (12 months of progression free survival). Besides, no significant side-effects was observed. Due to the current paucity of data on the combination of anlotinib and tislelizumab for advanced urothelial carcinoma, this study paves the way for further exploration of this combinatorial treatment strategy as a secondline therapy for advanced urothelial carcinoma.