| First Author | Liu Y | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 3 | Pages | 480-494.e7 |
| PubMed ID | 29533786 | Mgi Jnum | J:258625 |
| Mgi Id | MGI:6144237 | Doi | 10.1016/j.ccell.2018.02.005 |
| Citation | Liu Y, et al. (2018) Tumor-Repopulating Cells Induce PD-1 Expression in CD8(+) T Cells by Transferring Kynurenine and AhR Activation. Cancer Cell 33(3):480-494.e7 |
| abstractText | Despite the clinical successes fostered by immune checkpoint inhibitors, mechanisms underlying PD-1 upregulation in tumor-infiltrating T cells remain an enigma. Here, we show that tumor-repopulating cells (TRCs) drive PD-1 upregulation in CD8(+) T cells through a transcellular kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) pathway. Interferon-gamma produced by CD8(+) T cells stimulates release of high levels of Kyn produced by TRCs, which is transferred into adjacent CD8(+) T cells via the transporters SLC7A8 and PAT4. Kyn induces and activates AhR and thereby upregulates PD-1 expression. This Kyn-AhR pathway is confirmed in both tumor-bearing mice and cancer patients and its blockade enhances antitumor adoptive T cell therapy efficacy. Thus, we uncovered a mechanism of PD-1 upregulation with potential tumor immunotherapeutic applications. |
