We are thrilled that our recent study lead by @BayerlFelix is out in @ImmunityCP today. We addressed the question how cDC1 dysfunction is regulated in tumors and to which extent this contributes to cancer immune evasion. It is Open Access!👇
cell.com/immunity/fulltext/S…
A short 🧵:
Jun 13, 2023 · 3:13 PM UTC
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In our study, we find that PGE2, a bioactive lipid produced by many mouse and human cancers, drives immune evasion by rendering cDC1 dysfunctional, foremost with respect to their ability to communicate with tumor-infiltrating CD8+ T cells.
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How is this achieved? Our data suggest that PGE2 targets the transcription factor IRF8 in intratumoral cDC1, disabling the local orchestration of anti-cancer CD8+ T cell responses in the TME. This indicates a role for IRF8 in differentiated cDC1, beyond its role in DC development
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We went on and identified PGE2 signaling through the PGE2 receptors EP2/EP4 responsible for cDC1 dysfunction. Strikingly, ablation of EP2 and EP4 on cDC1 prevented their dysfunction in tumors, permitting cDC1 to instruct effective CD8+ T cell responses that achieve tumor control.
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Of note, our data indicate that this inhibitory mechanisms similarly applies to cDC1 dysfunction in human tumors. It may therefore be explored as target for novel cancer therapies aiming at promoting more effective anti-cancer immune responses in tumor tissue.
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We hope that our findings are of interest to many researchers in the field of immunology and oncology, especially those interested in harnessing the power of DCs for cancer therapy
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We are very greatful for the fantatstic support not only by the entire lab but also many fantastic colleagues and collaboration partners, including @buschraml @VeitBuchholz @AlfredZippelius @obenaufa and generous funding from @dfg_public and the EliteNetwork of Bavaria.
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Thanks also to Matthew Brown @matt_brown04, Michelle Tran @michelle_a_tran and Nina Bhardwaj @BhardwajLab for highlighting our key findings in their preview 💫: cell.com/immunity/fulltext/S…
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