| First Author | Lin H | Year | 2021 |
| Journal | Cancer Cell | Volume | 39 |
| Issue | 4 | Pages | 480-493.e6 |
| PubMed ID | 33513345 | Mgi Jnum | J:304131 |
| Mgi Id | MGI:6694726 | Doi | 10.1016/j.ccell.2020.12.023 |
| Citation | Lin H, et al. (2021) Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance. Cancer Cell 39(4):480-493.e6 |
| abstractText | Immunotherapy induces durable clinical responses in a fraction of patients with cancer. However, therapeutic resistance poses a major challenge to current immunotherapies. Here, we identify that expression of tumor stanniocalcin 1 (STC1) correlates with immunotherapy efficacy and is negatively associated with patient survival across diverse cancer types. Gain- and loss-of-function experiments demonstrate that tumor STC1 supports tumor progression and enables tumor resistance to checkpoint blockade in murine tumor models. Mechanistically, tumor STC1 interacts with calreticulin (CRT), an "eat-me" signal, and minimizes CRT membrane exposure, thereby abrogating membrane CRT-directed phagocytosis by antigen-presenting cells (APCs), including macrophages and dendritic cells. Consequently, this impairs APC capacity of antigen presentation and T cell activation. Thus, tumor STC1 inhibits APC phagocytosis and contributes to tumor immune evasion and immunotherapy resistance. We suggest that STC1 is a previously unappreciated phagocytosis checkpoint and targeting STC1 and its interaction with CRT may sensitize to cancer immunotherapy. |
