The following is a summary of “Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors” published in the November 2022 issue of Clinical Cancer by IJzendoorn et al.

A substantial component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a limited number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. It was hypothesized that neoplastic cells would be activated by CSF1R expressed on their surface, creating an autocrine loop. In this work, researchers examine cellular interactions in TGCT by means of single-cell RNA sequencing (scRNA-seq). A total of 18,788 single cells from 3 TGCT and 2 giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The 3 TGCTs were additionally examined utilizing long-read RNA sequencing. 

Investigators further confirmed and broadened the scRNA-seq results by using immunofluorescence and immunohistochemistry for a variety of markers. About 2 recurring neoplastic cell types were found in TGCT that are highly comparable to nonneoplastic synoviocytes. They found GFPT2 as a marker that reveals the neoplastic cells in TCGT. They found that CSF1R expression was absent in malignant cells. Study group found that the giant cells in TGCT and GCTB shared common MAB characteristics.

Neoplastic cells in TGCT look a lot like normal synoviocytes. The absence of CSF1R on tumor cells suggests they are resistant to standard treatment. When the YAP1/TAZ pathway is activated, GFPT2 is highly expressed in neoplastic cells. Also, they found that the neoplastic cells expressed the platelet-derived growth factor receptor. These findings reveal 2 more routes to target in this tumor.