| First Author | Bayerl F | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 6 | Pages | 1341-1358.e11 |
| PubMed ID | 37315536 | Mgi Jnum | J:341046 |
| Mgi Id | MGI:7495418 | Doi | 10.1016/j.immuni.2023.05.011 |
| Citation | Bayerl F, et al. (2023) Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses. Immunity 56(6):1341-1358.e11 |
| abstractText | Type 1 conventional dendritic cells (cDC1s) are critical for anti-cancer immunity. Protective anti-cancer immunity is thought to require cDC1s to sustain T cell responses within tumors, but it is poorly understood how this function is regulated and whether its subversion contributes to immune evasion. Here, we show that tumor-derived prostaglandin E2 (PGE(2)) programmed a dysfunctional state in intratumoral cDC1s, disabling their ability to locally orchestrate anti-cancer CD8(+) T cell responses. Mechanistically, cAMP signaling downstream of the PGE(2)-receptors EP2 and EP4 was responsible for the programming of cDC1 dysfunction, which depended on the loss of the transcription factor IRF8. Blockade of the PGE(2)-EP2/EP4-cDC1 axis prevented cDC1 dysfunction in tumors, locally reinvigorated anti-cancer CD8(+) T cell responses, and achieved cancer immune control. In human cDC1s, PGE(2)-induced dysfunction is conserved and associated with poor cancer patient prognosis. Our findings reveal a cDC1-dependent intratumoral checkpoint for anti-cancer immunity that is targeted by PGE(2) for immune evasion. |
