Poliovirus receptor and CD96 mediate trogocytosis between cancer cells and lymphocytes 2385

Description Trogocytosis, a bidirectional membrane exchange between cells, plays a crucial role in tumor-immune cell interactions. This process can promote cancer cell immune evasion through antigen loss, increase immune cell susceptibility to fratricide. Our research explores the involvement of poliovirus receptor (PVR) and its associated receptors in trogocytosis. We found that PVR enhances CD8+ T cell adhesion to ICAM-1, which, combined with TCR signaling, facilitates the acquisition of cell surface proteins via trogocytosis. Our study identifies CD96 as the primary PVR receptor mediating PVR transfer to CD8+ T cells. Mutational analysis implies crucial role of the PVR IgV domain in this transfer, with Q63 and F128 as key amino acids involved in the interaction. PVR transfer was observed at endogenous expression levels and confirmed by expression of labeled recombinant PVR in cancer cells. PVR-mediated trogocytosis was observed across six different tumor cell lines with varied basal PVR expression when interacting with CD8+ T cells. Also, PVR transfer was observed from PVR-overexpressing cancer cells to various activated and naïve T cell subsets, suggesting broad significance in cancer cell-immune cell communication. Moreover, trogocytosis inhibitor latrunculin A blocked the transfer of PVR. These findings suggest PVR is critical in cancer cell-immune cell communication. Thus, PVR-CD96 axis can be targeted to overcome immune evasion strategies and improve existing immunotherapies.