Valeria Fumagalli

💡 Excited to share a "News and Views" in @NatImmunol spearheaded by @frarro1 on a fascinating study by Heim et al. revealing a unique subset of CD8+ T cells in chronic #HBV infection that retains cytotoxic functions, challenging the classical view of T cell exhaustion. nature.com/articles/s41590-0… 🧵 (1/6) 2/ 🧬 These HBV-specific CD8+ T cells, identified via single-cell RNA sequencing, exhibit cytotoxic capabilities despite an attenuated state driven by TGF-β signaling—suggesting a new layer of immune control in chronic infections. 3/ 🔍 Interestingly, this echoes findings from our recent @CellCellPress paper, where we showed that CD8+ T cells in chronic #HBV infection don’t fit the classical exhaustion model either 4/ 💡 The study by Heim et al. suggests that targeting TGF-β signaling might rejuvenate these cytotoxic T cells, offering new therapeutic avenues for chronic #HBV infection. Could this be a step towards more effective immunotherapies? 5/ 🙏 Kudos to the research team for this significant contribution to our understanding of T cell heterogeneity in chronic infections. Check out our commentary here: nature.com/articles/s41590-0…; and the Heim et al. study here: nature.com/articles/s41590-0…. And revisit our related @CellCellPress paper here: cell.com/cell/fulltext/S0092… 6/ 🔗 Looking forward to your thoughts on these evolving insights into T cell dynamics! @ERC, @AIRC_it, @EMBO_YIP, @ArmeniseHarvard,@SanRaffaeleMI, @MyUniSR, @ICE_HBV, @HepBFoundation, @EASLnews, @AASLDtweets

💡Exciting news! Our latest research is now published in @CellCellPress: "Therapeutic potential of co-signaling receptor modulation in hepatitis B" 🚀🧵(1/11) 🔬Using mouse models, we traced the development and fate of dysfunctional CD8+ T cells, showing that hepatocellular priming induces a unique dysfunctional program distinct from classical exhaustion. (2/11) 🌟Key finding: Blocking co-inhibitory receptors like PD-1, CTLA-4, and LAG-3 showed minimal effect. However, activating 4-1BB and OX40 transformed dysfunctional CD8+ T cells into antiviral effectors. (3/11) 📊Prolonged antigenic stimulation leads to a self-renewing, long-lived population of CD8+ T cells with a unique transcriptional profile, including progenitor/stem-like and tissue-resident memory cells. (4/11) 📌In chronic settings, only 4-1BB maintained expression across all dysfunctional subsets, making it a prime candidate for therapeutic intervention in chronic HBV. (5/11) 🧬In HBeAg+ chronic patients, 4-1BB activation showed the highest potential to rejuvenate dysfunctional CD8+ T cells, making it a prime candidate for therapeutic intervention. (6/11) 🔑Our findings suggest that targeting all dysfunctional T cells, rather than only stem-like precursors, holds promise for treating chronic HBV infection. (7/11) 💡Mechanistic insights: 4-1BB activation enhances effector molecule expression and CD8+ T cell cytotoxicity, driving robust antiviral responses. (8/11) 🔍This study provides a comprehensive atlas of the co-signaling receptors induced in dysfunctional HBV-specific CD8+ T cells and reveals potential targets for therapeutic intervention. (9/11) 👏Huge thanks to our incredible team and collaborators, especially @frarro1, @Chiara_Laura91, Micol Ravà, @CaroCKrueger, @FichtMaria, Keigo Kawashima, and @CristianBecc who co-led the study. This work wouldn't be possible without you! (10/11) 📖Dive deeper into our study and its implications for HBV treatment. We're excited to hear your thoughts and engage in discussions! Full paper here: authors.elsevier.com/sd/arti… 💬📚 (11/11) @SanRaffaeleMI @MyUniSR @ERC_Research @AIRC_it @EMBO_YIP @ArmeniseHarvard

We will have an open PhD position in our lab in 2025 in the framework of this exciting Doctoral Network. Apply 👇

🎉Thrilled to announce that our project on reprogramming immune cells to fight chronic hepatitis B has been honored with an ERC Advanced Grant #ERCAdG! Our grant aims to redefine liver immunology and transform our battle against viral infections. 🧬💡 I'm deeply grateful to both current and past members of our lab for their exceptional dedication and hard work. It's truly thanks to their collective effort that we have been able to achieve such significant results. Equally, if not more, proud of my former PhD students @MarcoDegiov89, @inversodonato, and @ValeFuma91 for securing their own ERC grants (StG, CoG, and SyG, respectively) in the same call. 🌟 Stay tuned for groundbreaking insights! 🚀 #ScienceTwitter @ERC_Research @SanRaffaeleMI @MyUniSR europa.eu/!TkwhWc

The power of T cells minus antibodies - thanks Thi H. O. Nguyen & @KatherineKedz for a thoughtful commentary on our paper! nature.com/articles/s41590-0…