Publikationer pr. år
Publikationer pr. år
Mike B. Barnkob, Yale S. Michaels, Violaine André, Philip S. Macklin, Uzi Gileadi, Salvatore Valvo, Margarida Rei, Corinna Kulicke, Ji-Li Chen, Vitul Jain, Victoria K. Woodcock, Huw Colin-York, Andreas V. Hadjinicolaou, Youxin Kong, Viveka Mayya, Julie M. Mazet, Gracie-Jennah Mead, Joshua A. Bull, Pramila Rijal, Christopher W. Pugh
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
Semaphorin-3A (SEMA3A) functions as a chemorepulsive signal during development and can affect T cells by altering their filamentous actin (F-actin) cytoskeleton. The exact extent of these effects on tumour-specific T cells are not completely understood. Here we demonstrate that Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 are upregulated on stimulated CD8 + T cells, allowing tumour-derived SEMA3A to inhibit T cell migration and assembly of the immunological synapse. Deletion of NRP1 in both CD4 + and CD8 + T cells enhance CD8 + T-cell infiltration into tumours and restricted tumour growth in animal models. Conversely, over-expression of SEMA3A inhibit CD8 + T-cell infiltration. We further show that SEMA3A affects CD8 + T cell F-actin, leading to inhibition of immune synapse formation and motility. Examining a clear cell renal cell carcinoma patient cohort, we find that SEMA3A expression is associated with reduced survival, and that T-cells appear trapped in SEMA3A rich regions. Our study establishes SEMA3A as an inhibitor of effector CD8 + T cell tumour infiltration, suggesting that blocking NRP1 could improve T cell function in tumours.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 3173 |
Tidsskrift | Nature Communications |
Vol/bind | 15 |
Antal sider | 18 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 12. apr. 2024 |
Publikation: Bidrag til tidsskrift › Kommentar/debat › Forskning › peer review