Trogocytosis and Horizontal Gene Transfer Between Immune Cells and Renal Cancer Cells Alters Tumor Cell Gene Transcription and Is Promoted by Mer Signaling

Abstract

Trogocytosis is an underappreciated phenomenon that has been shown to play an important role in many aspects of both normal physiology and oncogenesis. The transfer of surface membrane fragments from infiltrating immune cells to tumor cells can have profound effects on tumor progression, immune evasion, and treatment efficacy. These studies demonstrate how trogocytosis and horizontal gene transfer between immune cells and renal cancer cells results in phenotypic changes in cancer cells. These changes result in expression of immune-specific proteins (such as CD45) on the surface of cancer cells. In addition to changes at the protein level, we also observed that internal cellular components such as genomic DNA can be transferred to cancer cells through physical contact. This transfer can induce changes to gene transcription that create a new cancer cell phenotype with access to previously inaccessible immune cell protein expression. Finally, we provide evidence that the Mer tyrosine kinase receptor is a key regulator of trogocytosis in renal cancer cells. This is significant because previously, no specific mechanism of trogocytosis had been identified. This work illustrates the complexity of the tumor-immune microenvironment and may provide the foundation for future therapeutic strategies that target trogocytosis to improve treatment efficacy.