Barnkob MB., Michaels YS., André V., Macklin PS., Gileadi U., Valvo S., Rei M., Kulicke C., Chen J-L., Jain V., Woodcock V., Colin-York H., Hadjinicolaou AV., Kong Y., Mayya V., Bull JA., Rijal P., Pugh CW., Townsend AR., Olsen LR., Fritzsche M., Fulga TA., Dustin ML., Jones EY., Cerundolo V.

<jats:title>ABSTRACT</jats:title><jats:p>Semaphorin-3A (Sema3A) regulates tumor angiogenesis, but its role in modulating anti-tumor immunity is unclear. We demonstrate that Sema3A secreted within the tumor microenvironment (TME) suppresses tumor-specific CD8+ T cell function via Neuropilin-1 (NRP1), a receptor that is upregulated upon activation with T cells’ cognate antigen. Sema3A inhibits T cell migration, assembly of the immunological synapse, and tumor killing. It achieves these functional effects through hyper-activating the acto-myosin system in T cells leading to cellular paralysis. Finally, using a clear cell renal cell carcinoma patient cohort, we demonstrate that human tumor-specific CD8+ T cells express NRP1 and are trapped in Sema3A rich regions of tumors. Our study establishes Sema3A as a potent inhibitor of anti-tumor immunity.</jats:p>

Semaphorin 3A induces cytoskeletal paralysis in tumor-specific CD8+ T cells

Barnkob MB., Michaels YS., André V., Macklin PS., Gileadi U., Valvo S., Rei M., Kulicke C., Chen J-L., Jain V., Woodcock V., Colin-York H., Hadjinicolaou AV., Kong Y., Mayya V., Bull JA., Rijal P., Pugh CW., Townsend AR., Olsen LR., Fritzsche M., Fulga TA., Dustin ML., Jones EY., Cerundolo V.

DOI

Type

Publisher

Publication Date