Abstract
Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. With technological developments and protocol refinements, single-cell approaches have become powerful tools that provide unprecedented insights into the kaleidoscopic tumor microenvironment and intricate cell-cell communications. In this review, we summarize recent applications of single-cell analysis in characterizing the UBC multicellular ecosystem, and discuss how to leverage the high-resolution information for more effective immune-based therapies.
Highlights
Urothelial bladder cancer (UBC) accounts for more than half a million new diagnoses and 212,536 deaths annually [1]
non-muscle invasive bladder cancer (NMIBC) refer to neoplasms staged as Ta, T1, or CIS, and are usually managed with TURBT followed by a single dose of intravesical chemotherapy to kill free-floating tumor cells
Given that immune checkpoint inhibitors (ICIs) may further augment the immune response triggered by radiotherapy-induced tumor cell death [5], several studies are evaluating the potential synergy between chemoradiation and immunotherapy, including KEYNOTE992 and SWOG S1806, two phase III randomized trials investigating ICIs in bladder-sparing treatment of Muscle invasive bladder cancer (MIBC) [4, 54, 55]
Summary
Urothelial bladder cancer (UBC) accounts for more than half a million new diagnoses and 212,536 deaths annually [1]. Extensive studies have been focused on dissecting the cellular and molecular mechanisms underlying the immune response of UBC, in order to identify clinical biomarkers to predict ICI treatment efficacy, and to design novel single or combination trials of more effective regimens [15,16,17]. The emerging single-cell technologies, along with blossoming bioinformatic tools, promise to provide a highresolution tumor immune landscape and exert a prominent impact on the field of UBC immunotherapy. We update the current progress of cancer immunotherapy in UBC, summarize the applications of cutting-edge single-cell analysis in decoding the tumor multicellular ecosystem, and discuss future prospects for using these high-dimensional multi-faceted data to guide more effective immune checkpoint therapies
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