Percutaneous ablative cryoimmunotherapy for micrometastaic abscopal effect: No complications

Abstract

Recent studies have shown efficacy of nivolumab, a monoclonal antibody specific for an immunoregulatory protein termed programmed death 1 (PD-1), against metastatic renal cell carcinoma. PD-1 is a transmembrane protein expressed on T cells that suppresses activation upon binding to its ligands, which may be secreted paraneoplastically by various cancers. Inhibition of PD-1 signaling via nivolumab may sensitize tumor-specific T lymphocytes in the immunosuppressive tumor microenvironment. Systemic elimination of micrometastases requires robust activation and proliferation of tumor antigen stimulated T cells. Cryoablation lyses tumor cell membranes but leaves intracellular tumor antigens intact for recognition by effectors systemically, while eliminating permissive T cell subtypes locally. This single case report describes CT-guided percutaneous cryoablation of a metastatic renal cell carcinoma with local administration of nivolumab to simultaneously debulk the primary tumor, sensitize effector T cells against tumor antigens, and augment the systemic immune response elicited against established metastases. One month follow up PET scan revealed decreased uptake in the two smaller metastatic bone lesions with the smallest lesion completely eliminated. The largest metastatic bone lesion was slightly decreased in size and exhibited slightly increased uptake. The patient's presenting complaint of hip pain was abrogated, allowing her to resume independent ambulation. CT-guided percutaneous cryoablation is minimally invasive and preserves tumor antigens, which are subsequently presented to tumor-specific T cells; their differentiation into cytotoxic T cells may be guided and their proliferation may be augmented by local administration of immunostimulatory pharmacotherapy at the time of the procedure.