Renal Cancer Tissue after Nivolumab/Ipilimumab Combination Therapy for Metastatic Renal Cell Carcinoma

Abstract

Antibodies that inhibit the function of PD-1, PD-L1, and CTLA4 increase the tumor immune response and suppress tumor growth. These immune checkpoint inhibitors have also been introduced into the treatment of metastatic renal cancer. We report combination therapywith nivolumab and ipilimumab in a case of renal cancer with bone metastasis and subsequent removal of the primarytumor. The patient was a 67-year-old male. Computed tomography (CT) revealed a 6.5×5.6 cm renal tumor in the left kidney, with osteolytic metastasis to the left 11th rib and thoracic spine. Irradiation of 30 Gy was performed for the thoracic spine tumors. Then, nivolumab+ipilimumab combination therapywas continued for a total of 4 courses. In addition, 4 courses of nivolumab monotherapywere added. CT after therapyrevealed a 15. 4% decrease in the length-wise diameter and increase in internal necrosis in the left kidneytumor, as well as shrinkage, absorption reduction, and appearance of a hardened border in the bone metastasis. Therefore, transabdominal left nephrectomywas performed. The histopathological diagnosis was clear cell carcinoma pT1bN0, grade 2. The renal cancer tissue was mostlyinternal necrosis, and the viable tumor comprised approximately10%. Marked infiltration of predominantlyCD8-positive lymphocytes to the primarytumor site was observed. Postoperatively, nivolumab was discontinued and the patient is under observation. In the specimens from 2 patients treated using pazopanib, a tyrosine kinase inhibitor, prior to renal cell cancer removal, there were fewer CD8- and CD4-positive cells infiltrating the renal cancer than after the combination therapy.