Decoding the genomic identity of candidate tumor-leukocyte hybrid cells in circulation [RNA]

However, existing evidence relies on staining, and without molecular profiling, their prevalence, true identity, and the extent of their immune-like features remain unclear. To address this, we developed a mouse melanoma model with distinct fluorescent markers introduced into cancer and host cells, enabling isolation of dual-positive (DP) cells as candidates for fusion.

We characterized these cells using imaging FACS to visualize cytoplasmic merging together with single-cell whole-genome and transcriptome co-profiling to detect tumor or host-specific genomic variants and gene-expression profiles. Among 500 profiled DPs, we found no clear evidence of fusion events. Only two cells in lung-metastases displayed both macrophage- and tumor-features, consistent with potential fusion but also with early stages of phagocytosis.