| First Author | Schmassmann P | Year | 2023 |
| Journal | Sci Transl Med | Volume | 15 |
| Issue | 705 | Pages | eadf5302 |
| PubMed ID | 37467314 | Mgi Jnum | J:343619 |
| Mgi Id | MGI:7567533 | Doi | 10.1126/scitranslmed.adf5302 |
| Citation | Schmassmann P, et al. (2023) Targeting the Siglec-sialic acid axis promotes antitumor immune responses in preclinical models of glioblastoma. Sci Transl Med 15(705):eadf5302 |
| abstractText | Glioblastoma (GBM) is the most aggressive form of primary brain tumor, for which effective therapies are urgently needed. Cancer cells are capable of evading clearance by phagocytes such as microglia- and monocyte-derived cells through engaging tolerogenic programs. Here, we found that high expression of sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) correlates with reduced survival in patients with GBM. Using microglia- and monocyte-derived cell-specific knockouts of Siglec-E, the murine functional homolog of Siglec-9, together with single-cell RNA sequencing, we demonstrated that Siglec-E inhibits phagocytosis by these cells, thereby promoting immune evasion. Loss of Siglec-E on monocyte-derived cells further enhanced antigen cross-presentation and production of pro-inflammatory cytokines, which resulted in more efficient T cell priming. This bridging of innate and adaptive responses delayed tumor growth and resulted in prolonged survival in murine models of GBM. Furthermore, we showed the combinatorial activity of Siglec-E blockade and other immunotherapies demonstrating the potential for targeting Siglec-9 as a treatment for patients with GBM. |
