Other
13 Authors
- Bosenberg M,
- Fang D,
- Tian J,
- Muzumdar MD,
- Wu L,
- Khan S,
- Zhang D,
- Kurbatov V,
- Yan Q,
- Wang Y,
- Lu J,
- Lu Q,
- Wang Q
| First Author | Tian J | Year | 2021 |
| Journal | EMBO J | Volume | 40 |
| Issue | 7 | Pages | e106065 |
| PubMed ID | 33615517 | Mgi Jnum | J:354730 |
| Mgi Id | MGI:7736394 | Doi | 10.15252/embj.2020106065 |
| Citation | Tian J, et al. (2021) 5-Fluorouracil efficacy requires anti-tumor immunity triggered by cancer-cell-intrinsic STING. EMBO J 40(7):e106065 |
| abstractText | 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug, but the mechanisms underlying 5-FU efficacy in immunocompetent hosts in vivo remain largely elusive. Through modeling 5-FU response of murine colon and melanoma tumors, we report that effective reduction of tumor burden by 5-FU is dependent on anti-tumor immunity triggered by the activation of cancer-cell-intrinsic STING. While the loss of STING does not induce 5-FU resistance in vitro, effective 5-FU responsiveness in vivo requires cancer-cell-intrinsic cGAS, STING, and subsequent type I interferon (IFN) production, as well as IFN-sensing by bone-marrow-derived cells. In the absence of cancer-cell-intrinsic STING, a much higher dose of 5-FU is needed to reduce tumor burden. 5-FU treatment leads to increased intratumoral T cells, and T-cell depletion significantly reduces the efficacy of 5-FU in vivo. In human colorectal specimens, higher STING expression is associated with better survival and responsiveness to chemotherapy. Our results support a model in which 5-FU triggers cancer-cell-initiated anti-tumor immunity to reduce tumor burden, and our findings could be harnessed to improve therapeutic effectiveness and toxicity for colon and other cancers. |
