Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma

p53 蛋白的表达与 GATA3/CR5/6 阴性复发性非肌层浸润性膀胱尿路上皮癌人源异种移植模型中的抗 PD-L1 治疗反应相关

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作者:Ekaterina Blinova, Elena Samishina, Olga Deryabina, Dmitry Blinov, Dmitry Roshchin, Evgeniia Shich, Oxana Tumutolova, Ilya Fedoseykin, Anna Epishkina, Haydar Barakat, Andrey Kaprin, Kirill Zhandarov, Dmitrij Perepechin, Dmitrij Merinov, Gordey Brykin, Karen Arutiunian, Stanislav Serebrianyi, Artem M

Background

The possible involvement of p53 signaling, FGFR3 expression, and FGFR3 mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main

Conclusions

p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

Methods

twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones-low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals' survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and FGFR3 mutations in codons 248 and 249 were detected by real-time polymerase chain reaction.

Results

The expression of p53 protein is an independent factor affecting the animals' survival time [HR = 0.036, p = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and FGFR3 mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

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