Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma

Abstract

Background: Metastatic carcinoma of a renal allograft is a rare but life threatening event with a difficult clinical management. Recent reports suggested a potential role of BK polyomavirus (BKPyV) in the development of urologic tract malignancies in kidney transplant recipients. Case study: We investigated a kidney-pancreas female recipient with an history of BKPyV nephritis who developed a rapidly progressive and widely metastatic donor-derived renal carcinoma 9 years after transplantation. Histology and FISH analysis revealed a donor-derived (XY tumor cells) collecting (Bellini) duct carcinoma. The presence of BKPyV oncogenic large tumor antigen (LTag) was identified in large amount within the kidney tumor and the bowel metastases. Whole genome sequencing of the tumor confirmed multiple genome BKPyV integrations. The transplanted kidney was removed, immunosuppression was withdrawn, and recombinant interleukin-2 (IL-2) was administered for 3 months, inducing a complete tumor clearance, with no evidence of disease at 6-year follow-up. The immunological profiling during IL-2 therapy revealed the presence of donor-specific T cells and expanded cytokine-producing bright NK cells but no donor-specific antibodies. Finally, we found persistently elevated anti-BK virus IgG titers and a specific anti-BKPyV T cell response. Conclusion: This investigation showed evidence for the potential oncogenic role of BKPyV in collecting duct carcinoma in renal allografts and demonstrated that immunosuppression withdrawal and IL-2 therapy can lead to an efficient antitumor cellular mediated rejection possibly via 3 distinct mechanisms including (1) host-versus-graft, (2) host-versus-tumor and (3) anti-BKPyV responses.

Total nephroureterocystectomy and urethrectomy due to urothelial carcinoma associated with the BK polyomavirus infection after kidney transplantation: a case report with literature review

“…Recently, the relationship between BKPyV and genitourinary malignant tumor, such as urothelial carcinoma [10,11] especially in bladder cancer [11][12][13] and renal cell carcinoma [14], has been reported. However, few studies suggested a potential role of BKPyV in the development of urologic tract malignancies in KTx recipients [15], and the association remains controversial. Herein, we describe a case of a KTx recipient with positive urine BKPyV replication who developed a graft pelvic tumor with positive immunohistochemical staining for simian virus 40 large T antigen (SV40 TAg).…”

Variations in BK Polyomavirus Immunodominant Large Tumor Antigen-Specific 9mer CD8 T-Cell Epitopes Predict Altered HLA-Presentation and Immune Failure

“…Our recent work suggests that alarming innate and adaptive immune responses may be delayed in the late phase of BKPyV replication [ 17 ]. Finally, we speculate that LTag-targeted CD8 T-cell responses including those directed against the N-terminus shared with small T-antigen [ 37 ] may protect against BKPyV-associated urothelial carcinoma expressing solely LTag or truncated derivatives from chromosomally integrated BKPyV genomes [ 8 , 9 ], when there is little or no Vp1 expression [ 7 ].…”

“…BK polyomavirus (BKPyV) is an opportunistic pathogen causing polyomavirus-associated hemorrhagic cystitis (PyVHC) in 5–20% of allogeneic hematopoietic stem cell (HSCT) recipients [ 1 , 2 , 3 ] and polyomavirus-associated nephropathy (PyVAN) in 1–15% of kidney transplant (KT) patients [ 4 , 5 ]. Moreover, PyV-associated urothelial cancer (PyVUC) has been recognized as an emerging entity in immunosuppressed patients with a history of prolonged BKPyV-replication and nephropathy following accidental integration of the BKPyV genome into human host cell chromosomes [ 6 , 7 , 8 , 9 ]. Uncontrolled BKPyV replication due to insufficient BKPyV-specific immunity appears to be the common denominator of these three major BKPyV diseases [ 10 , 11 , 12 , 13 ].…”

Metastatic Donor-derived Malignancies Following Simultaneous Pancreas-kidney Transplant: Three Case Reports and Management Strategies

“…In their case, rejection of the pancreas resulted in a spontaneous rupture of a pseudoaneurysm of the pancreas arterial anastomosis requiring emergent surgery. 10 To our knowledge, there is no other literature on the successful treatment of metastatic donor-derived malignancy in SPK recipients.…”