| First Author | Sharma P | Year | 2024 |
| Journal | Science | Volume | 383 |
| Issue | 6679 | Pages | 190-200 |
| PubMed ID | 38207022 | Mgi Jnum | J:344620 |
| Mgi Id | MGI:7577531 | Doi | 10.1126/science.adg1955 |
| Citation | Sharma P, et al. (2024) Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape. Science 383(6679):190-200 |
| abstractText | Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor-beta (TGF-beta) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy. |
