journal contribution
posted on 2025-10-15, 07:23 authored by Zhaopei Liu, Lingkai Zhang, Kaifeng Jin, Han Zeng, Xiaohe Su, Yawei Ding, Jiaxing Sun, Yuzhen Wu, Hailong Liu, Yu Zhu, Le Xu, Weijuan Zhang, Zewei Wang, Yuan Chang, Jiejie Xu <p>Enrollment, clinicopathological features and inclusion criteria for ZSHS, FUSCC, and Shanghai-sequencing cohorts.</p>
Funding
National Natural Science Foundation of China (NSFC)
China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)
Natural Science Foundation of Shanghai Municipality (上海市自然科学基金)
Shanghai Sailing Program
Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission
Shanghai Municipal Health Bureau (Shanghai Municipal Public Health Bureau)
Beijing Xisike Clinical Oncology Research Foundation (CSCO Foundation)
Fudan University Shanghai Cancer Center for Outstanding Youth Scholars Foundation
Shanghai Anticancer Association EYAS PROJECT
Youth Foundation of Zhongshan Hospital affiliated with Fudan University
Chongqing Postdoctoral Program for Innovative Talents
Key Project of Young Doctor Incubation Program of the Second Affiliated Hospital of Army Medical University
History
ARTICLE ABSTRACT
ARID1A, encoding a component of the switch/sucrose nonfermentable complex, is frequently mutated in urothelial carcinoma. However, its specific impacts on clinical outcomes and CD8+ T-cell functions in urothelial carcinoma remain poorly understood.
The clinical relevance of ARID1A loss and CD8+ T-cell infiltration was evaluated in three cohorts [Zhongshan Hospital, Fudan University (ZSHS), n = 135; Fudan University Shanghai Cancer Center (FUSCC), n = 118; and IMvigor210, n = 274]. Immune microenvironment profiling was performed via IHC in the ZSHS cohort and transcriptomics in the IMvigor210 cohort. The Shanghai-sequencing cohort (n = 134) provided genomic characterization of ARID1A-loss patients.
ARID1A loss did not affect overall survival and CD8+ T-cell infiltration in both ZSHS and FUSCC cohorts. Only in ARID1A-loss urothelial carcinoma, high infiltration of CD8+ T cells yielded favorable outcomes (ZSHS cohort, log-rank P = 0.010; FUSCC cohort, log-rank P = 0.015). Moreover, ARID1Aloss CD8high patients displayed improved survival following adjuvant chemotherapy (log-rank P = 0.015) and PD-1/PD-L1 blockade (log-rank P = 0.020). In ARID1A-loss urothelial carcinoma, the enhanced antitumor function of CD8+ T cells might be affected by tertiary lymphoid structures. Furthermore, ARID1Aloss CD8high patients exhibited an antitumor immune contexture characterized by decreased immune-suppressive cells such as DC-SIGN+ tumor-associated macrophages, PDPN+ cells, and TGF-β+ cells, as well as lower expression of checkpoints such as B7-H3 and B7-H4.
The combination of ARID1A loss plus CD8+ T-cell infiltration indicated a favorable prognosis and responsiveness to both chemotherapy and immunotherapy. These findings provide valuable insights for developing novel therapeutic strategies and improving treatment stratification for urothelial carcinoma.
