| First Author | Sun R | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 34 | Pages | eadd7399 |
| PubMed ID | 37611111 | Mgi Jnum | J:339265 |
| Mgi Id | MGI:7521513 | Doi | 10.1126/sciadv.add7399 |
| Citation | Sun R, et al. (2023) Amphiregulin couples IL1RL1(+) regulatory T cells and cancer-associated fibroblasts to impede antitumor immunity. Sci Adv 9(34):eadd7399 |
| abstractText | Regulatory T (T(reg)) cells and cancer-associated fibroblasts (CAFs) jointly promote tumor immune tolerance and tumorigenesis. The molecular apparatus that drives T(reg) cell and CAF coordination in the tumor microenvironment (TME) remains elusive. Interleukin 33 (IL-33) has been shown to enhance fibrosis and IL1RL1(+) T(reg) cell accumulation during tumorigenesis and tissue repair. We demonstrated that IL1RL1 signaling in T(reg) cells greatly dampened the antitumor activity of both IL-33 and PD-1 blockade. Whole tumor single-cell RNA sequencing (scRNA-seq) analysis and blockade experiments revealed that the amphiregulin (AREG)-epidermal growth factor receptor (EGFR) axis mediated cross-talk between IL1RL1(+) T(reg) cells and CAFs. We further demonstrated that the AREG/EGFR axis enables T(reg) cells to promote a profibrotic and immunosuppressive functional state of CAFs. Moreover, AREG mAbs and IL-33 concertedly inhibited tumor growth. Our study reveals a previously unidentified AREG/EGFR-mediated T(reg)/CAF coupling that controls the bifurcation of fibroblast functional states and is a critical barrier for cancer immunotherapy. |
