Metachronous bilateral renal cancer with immune checkpoint blockade-mediated eradication of bone metastasis: case...

The immune landscape of renal cell carcinoma (RCC) is a key determinant of response to immune checkpoint inhibitors (ICIs). Yet, direct comparisons of immune infiltrates across histologic subtypes and metastatic sites within the same patient are rarely possible.

A 71-year-old man underwent left-sided nephrectomy for clear cell RCC (ccRCC) in 2013. He developed a right-sided renal and liver-capsule lesion in 2024, with an enlarged paracaval lymph node. Partial right-sided nephrectomy, liver resection, and lymphadenectomy confirmed RCC with prominent sarcomatoid histology (sRCC). Chest CT and pelvic MRI scan did not detect metastases, but the cervical spine was not explored due to lack of symptoms. Two cycles of nivolumab plus ipilimumab were performed before discovering severe cervical spine pain. MRI identified a previously missed metastasis to the C4 vertebral body. Corpectomy achieved nearly complete tumor resection supplemented with fusion. Immunohistochemistry and multiplex immunofluorescence for PD-L1/CD3/CD20/CD163/C5aR1/CD31/CA9 were performed on primary tumors and metastases.

Here we show (1) robust CD3⁺ and CD20⁺ infiltration in primary tumors and metastases, with immune cells in direct contact with tumor cells or organized in lymphoid aggregates/tertiary lymphoid structures; (2) PD-L1 overexpression in sRCC and nodal metastasis but absent in post-immunotherapy bone lesions; (3) increased CD163⁺ macrophages in sRCC and metastases versus ccRCC.

This case illustrates that ICIs can induce near-complete eradication of bone metastases; that bone is not an immune-exempt organ, with massive intratumoral immune cell infiltration; and that immediate immune-mediated tumor clearance prevents structural skeletal damage, which merits careful surveillance.