Single-Cell Phenotyping of CD73 Expression Reveals the Diversity of the Tumor Immune Microenvironment and Reflects the Prognosis of Bladder Cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18151
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Keio University
• Principal Investigator: Izawa Mizuki 慶應義塾大学, 医学部(信濃町), 助教 (80868761)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膀胱癌 / CD73 / 癌微小環境

Outline of Final Research Achievements

We focused on expression of CD73 to clarify the state of CD73 positivity in bladder cancer (BCa) immunity. We utilized clinical tissue microarrays of human BCa and simultaneously performed fluorescent staining of cell type-specific markers (CD3, CD8, Foxp3, PD-1, and PD-L1) and CD73 together with DAPI. In total, 156 subjects were included. Multiplexed cellular imaging revealed a unique interaction between CD73 expression and CD8+ cytotoxic T cells (CTLs) and Foxp3+ Treg cells in human BCa, showing the high infiltration of CD8+CD73+ CTLs and Foxp3+CD73+ Treg cells in tumors to be associated with tumorigenesis and poor prognosis in BCa. In conclusion, the present results on the status of CD73 in cancer immunity suggest that CD73 expression on specific T-cell types has a negative immunoregulatory function. These findings may provide further insights into the immunobiological landscape of BCa, which may be translationally linked to improvements in future immunotherapy practice.

Free Research Field

膀胱癌

Academic Significance and Societal Importance of the Research Achievements

癌研究におけるCD73依存的な細胞外アデノシン代謝の役割は、多岐にわたる分野で注目されているが、膀胱癌領域における報告は少ない。本研究ではCD73の発現が現在臨床で用いられている膀胱癌治療との関連について着目した。近年の腫瘍免疫学の発展によって、膀胱癌はヒトの癌のなかでも遺伝子変異が多く、免疫チェックポイント阻害剤が有効であることは周知の事実となった。CD73を通して癌免疫応答を解明することで、BCG注入療法の治療効果予測因子を確立するのみならず、転移・切除不応性膀胱癌の臨床で用いられている抗PD-1/PDL-1抗体の適応や最適な免疫チェックポイント阻害剤の併用についても理解が進んだ。