| First Author | Tang Y | Year | 2021 |
| Journal | Cancer Discov | PubMed ID | 34193438 |
| Mgi Jnum | J:316210 | Mgi Id | MGI:6832731 |
| Doi | 10.1158/2159-8290.CD-20-0833 | Citation | Tang Y, et al. (2021) Tumor Microenvironment-Derived R-spondins Enhance Anti-Tumor Immunity to Suppress Tumor Growth and Sensitize for Immune Checkpoint Blockade Therapy. Cancer Discov |
| abstractText | Natural killer (NK) cells and T cells are key effectors of anti-tumor immune responses and major targets of checkpoint inhibitors. In multiple cancer types, we find that the expression of Wnt signaling potentiator R-spondin genes (e.g. RSPO3) is associated with favorable prognosis and is positively correlated with gene signatures of both NK cells and T cells. While endothelial cells and cancer-associated fibroblasts comprise the R-spondin3-producing cells, NK cells and T cells correspondingly express the R-spondin3 receptor LRG6 within the tumor microenvironment. Exogenous expression or intratumor injection of R-spondin3 in tumors enhanced the infiltration and function of cytotoxic effector cells, which led to tumor regression. NK cells and CD8+ T cells independently and cooperatively contributed to R-spondin3-induced control of distinct tumor types. The effect of R-spondin3 was mediated in part through upregulation of MYC and ribosomal biogenesis. Importantly, R-spondin3 expression enhanced tumor sensitivity to anti-PD1 therapy, thereby highlighting new therapeutic avenues. |
