Complete response to immune checkpoint blockade in sarcomatoid renal cell carcinoma with bone marrow metastasis: case...

Bone marrow represents a unique microenvironment enriched with both immunosuppressive cells and immune-activating functions. However, its role in metastasis and response to immunotherapy remains poorly understood. We report a case of sarcomatoid clear cell renal cell carcinoma with systemic bone marrow metastasis that achieved a complete response to ipilimumab plus nivolumab. Using matched pretreatment and post-treatment bone marrow samples, we performed integrative immune profiling. Pretreatment analyses showed abundant CD14⁺ myeloid cells, phenotypically consistent with myeloid-derived suppressor cell (MDSC)-like populations, together with CD8⁺ T cells. RNA-seq-based deconvolution revealed a predominance of monocytic-MDSC-like cells, which were selectively reduced after treatment with a shift toward monocyte and neutrophil-associated cells. Paired single-sample gene set enrichment analysis demonstrated that immunosuppressive (MDSC-like populations and TGF-β), and immune-activating (CD8⁺ T cell, interferon-gamma) pathways coexisted at baseline and were broadly attenuated following treatment. These findings suggest that the bone marrow microenvironment harbored a hybrid immune state characterized by concurrent inflammatory and immunosuppressive programs. The subsequent global contraction of both programs suggests that immune remodeling primarily reflects the resolution of tumor-driven immune activation following tumor eradication, rather than the effect from immune checkpoint inhibitors. This case highlights that even in an immune-restrictive niche, latent but functional antitumor immunity can be unleashed by immune checkpoint blockade.