Tumor immune microenvironment analysis and MRI results of a phase II trial investigating tislelizumab (T) in the neoadjuvant treatment of high-risk upper tract urothelial carcinoma (UTUC).

person Jiwei Huang Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China info_outline Jiwei Huang, Xinyun Cai, Cheoklong NG, Yuansheng Luo, Zaoyu Wang, Wen Kong, Jin Zhang, Yonghui Chen, Guangyu Wu, Haige Chen, Wei Xue

Authors person Jiwei Huang Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China info_outline Jiwei Huang, Xinyun Cai, Cheoklong NG, Yuansheng Luo, Zaoyu Wang, Wen Kong, Jin Zhang, Yonghui Chen, Guangyu Wu, Haige Chen, Wei Xue Organizations Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, Department of Radiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Renji Hospital Shanghai Jiaotong University School of Medicine, Dept. of Radiology, Shanghai, China, Department of Urology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Abstract Disclosures Research Funding No funding sources reported Background: Although PD-1/L1 checkpoint inhibitors have shown promising efficacy results in the neoadjuvant treatment of urothelial carcinoma, part of patients may have disease progression during the treatment. Up to now, there is no definitive biomarker to predict the response of neoadjuvant immunotherapy. We have formerly reported the preliminary results of T, a PD-1 checkpoint inhibitor, in the neoadjuvant treatment of UTUC. Herein, we report the tumor immune microenvironment analysis and contrast-enhanced MRI results to explore possible pathological and radiological characteristics in correlation with treatment response. Methods: Patients were given T 200mg IV every 3 weeks for at most 4 cycles followed by surgery (radical nephroureterectomy, ureteral resection or endoscopic ablation). The primary endpoint was pCR rate (ypT0N0). The secondary endpoints included pathological response rate (≤ypT1N0), objective response rate and safety. Contrast-enhanced MRI examination was performed before the third dose and another before the surgery and the apparent diffusion coefficient(ADC) was calculated. The infiltrating immune cells pattern within tumor microenvironment was analyzed using multiplexed immunofluorescence (mIF) staining on pretreatment samples. Results: Between Mar 2021 and Sep 2022, 16 patients were enrolled. 4 patients (25%) patients achieved pCR and 7 patients (43.8%) were re-staged as ≤ypT1N0 at specimens. Best of response was cPR in 6 patients, cSD in 7 patients and cPD in 3 patients. The density of PD-L1+CD68+ cells in the stromal region was significantly higher in cPR patients compared to cSD or cPD patients before neoadjuvant treatment (p=0.002). Additionally, the density of PD-1+CD8+ cells in the stromal region of cPR patients was also higher, although the significance was borderline (p=0.065). The average value of ADC showed no statistically significant difference between cPR patients and cSD or cPD patients (p=0.997). However, a significant higher entropy of ADC was found in cPR patients compared with cSD or cPD patients (p=0.002). Conclusions: The elevated ADC entropy on MRI and the enrichment of PD-L1+CD68+ cells within tumor microenvironment before treatment were observed in cPR patients. Both characteristics might help to identify UTUC patients who can benefit from neoadjuvant immune therapy. Clinical trial information: NCT04672330.

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