Clinical significance of blocking novel immune checkpoint B7-H4 in urothelial carcinoma of bladder as a potential therapeutic target

被引:1
作者
Raja, David [1 ]
Singh, Aishwarya [1 ]
Kurra, Santosh [1 ]
Nayak, Brusabhanu [3 ]
Kaushal, Seema [2 ]
Sharma, Alpana [1 ]
Singh, Prabhjot [3 ]
机构
[1] All India Inst Med Sci AIIMS, Dept Biochem, New Delhi, India
[2] All India Inst Med Sci AIIMS, Dept Pathol, New Delhi, India
[3] All India Inst Med Sci AIIMS, Dept Urol, New Delhi, India
关键词
Urothelial carcinoma of bladder; Muscle invasive/and Non-muscle invasive bladder cancer; Immune checkpoints; B7-H4; PD-L1; Immunotherapy; OPEN-LABEL; T-CELLS; CANCER; EXPRESSION; IMMUNOTHERAPY; CHEMOTHERAPY; CISPLATIN; SURVIVAL;
D O I
10.1007/s12032-024-02299-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Urothelial Carcinoma of Bladder is complex disease with high mortality and recurrence rates. Current standard regimes have exhibited anti-tumor activity but still, a proportion of patients are non-responsive or in-eligible to receive such treatments. Immune checkpoints have emerged as potential class of therapeutics to be tested in UCB patients. Clinical trials targeting PD-1/PD-L1 axis have been tested in UCB but still a proportion of patients are non-responsive to it which stresses upon identifying new targets. New immune checkpoint B7-H4 has been shown to negatively regulate T cell activity in cancer and is a poor prognostic factor in various solid tumors. In this study we assessed the novel immune checkpoint B7-H4 status in UCB patients. We observed elevated expression of B7-H4 and PD-L1 on CD8+ T cells in circulation of UCB patients. Relative mRNA expression and immunohistochemistry displayed upregulation in bladder tumor tissue. Increased expression of B7-H4 along with PD-L1 in periphery and tumor of UCB patients highlights involvement of B7-H4 in disease progression. Combinatorial blocking of B7-H4 and PD-L1 enhanced IFN-gamma and granzyme B in CD8+ T cells functional T cell immune response in UCB patients. Also, B7-H4 was significantly associated with clinico-pathological parameters. Our findings highlight B7-H4 as potential therapeutic target for treatment of UCB patients in future after further validation.
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页数:12
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