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J Immunother Cancer. 2019 Jun 3;7(1):144. doi: 10.1186/s40425-019-0607-z.

PD-L1 detection using 89Zr-atezolizumab immuno-PET in renal cell carcinoma tumorgrafts from a patient with favorable nivolumab response.

Author information

1
Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
2
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
4
Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
5
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
6
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
7
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
8
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
9
Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. guiyang.hao@utsouthwestern.edu.
10
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. guiyang.hao@utsouthwestern.edu.
11
Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. xiankai.sun@utsouthwestern.edu.
12
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. xiankai.sun@utsouthwestern.edu.
13
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. xiankai.sun@utsouthwestern.edu.
14
Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. james.brugarolas@utsouthwestern.edu.
15
Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. james.brugarolas@utsouthwestern.edu.

Abstract

BACKGROUND:

Programmed death-ligand 1 (PD-L1) expression in metastatic renal cell carcinoma (RCC) correlates with a worse prognosis, but whether it also predicts responsiveness to anti-PD-1/PD-L1 therapy remains unclear. Most studies of PD-L1 are limited by evaluation in primary rather than metastatic sites, and in biopsy samples, which may not be representative. These limitations may be overcome with immuno-positron emission tomography (iPET), an emerging tool allowing the detection of cell surface proteins with radiolabeled antibodies. Here, we report iPET studies of PD-L1 in a preclinical tumorgraft model of clear cell RCC (ccRCC) from a patient who had a favorable response to anti-PD-1 therapy.

CASE PRESENTATION:

A 49-year-old man underwent a cytoreductive nephrectomy in 2017 of a right kidney tumor invading into the adrenal gland that was metastatic to the lungs and a rib. Histological analyses revealed a ccRCC of ISUP grade 4 with extensive sarcomatoid features. IMDC risk group was poor. Within two hours of surgery, a tumor sample was implanted orthotopically into NOD/SCID mice. Consistent with an aggressive tumor, a renal mass was detected 18 days post-implantation. Histologically, the tumorgraft showed sarcomatoid differentiation and high levels of PD-L1, similar to the patient's tumor. PD-L1 was evaluated in subsequently transplanted mice using iPET and the results were compared to control mice implanted with a PD-L1-negative tumor. We labeled atezolizumab, an anti-PD-L1 antibody with a mutant Fc, with zirconium-89. iPET revealed significantly higher 89Zr-atezolizumab uptake in index than control tumorgrafts. The patient was treated with high-dose IL2 initially, and subsequently with pazopanib, with rapidly progressive disease, but had a durable response with nivolumab.

CONCLUSIONS:

To our knowledge, this is the first report of non-invasive detection of PD-L1 in renal cancer using molecular imaging. This study supports clinical evaluation of iPET to identify RCC patients with tumors deploying the PD-L1 checkpoint pathway who may be most likely to benefit from PD-1/PD-L1 disrupting drugs.

KEYWORDS:

IO; Immune checkpoint inhibitors; Immuno-PET; Immunotherapy; Kidney cancer; PD-1; PD-L1; PDX; Patient-derived xenograft; Predictive biomarkers; Renal cancer; SABR; SBRT

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