Inducing lymphoid niches across cancers by tumor-to-dendritic cell reprogramming — ASN Events
  1. Schedule
  2. Plenary 7: Translating DC Biology into Therapies: Vaccines & Beyond
  3. Inducing lymphoid niches across cancers by tumor-to-dendritic cell reprogramming

Inducing lymphoid niches across cancers by tumor-to-dendritic cell reprogramming (141373)

Filipe Pereira 1 2 3 4 5 , Ervin Ascic 1 2 6 , Camille Chatelain 1 2 , Gaia Fontanari 1 2 , César Pérez Bucio 1 2 , Linmeng Zhang 1 2 7 , Maria Thrasyvoulou 1 2 , Viktoria Karali 1 2 , Tommaso Ballocci 1 2 , Maria de Rosa Torres 1 2 , Simon Rabreau 1 2 , Katherine Hampton 1 2 , Martin Lauss 8 , Bengt Phung 8 , Fritiof Åkerström 3 , Arun Kumar Sundaramurthy 3 , Xavier Catena 3 , Chaofan Fan 1 2 , Stevanus Jonathan 9 , Anna Darabi 9 , Johan Bengzon 9 , Fábio F Rosa 3 , Göran B Jönsson 8 , Ilia Kurochkin 1 2
  1. Division of Immuno-Oncology, Science for Life Laboratory, Lund Stem Cell Center, Lund University, Lund, Sweden
  2. Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden
  3. Asgard Therapeutics AB, Medicon Village, Lund, Sweden
  4. CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
  5. CiBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
  6. CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
  7. State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hopsital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  8. Department of Clinical Sciences, Division of Oncology and Pathology, Lund University Cancer Center, Lund University, Lund, Sweden
  9. Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden

Tertiary lymphoid structures (TLS) in tumors are associated with improved responses to immunotherapy, but their controlled induction remains elusive. Here, we used in vivo reprogramming of tumor cells into type-1 conventional dendritic cell (cDC1)–like cells to rewire the tumor microenvironment and induce immunogenic TLS (imgTLS) across melanoma, colon, bladder, breast and pancreatic cancer models with distinct genetic backgrounds. cDC1-like cells activated lymphotoxin, TNF, and interferon programs, and engaged early with T cells through MHC-I and CD40 signaling to induce imgTLS containing BCL6⁺ germinal centers, independently of endogenous cDC1s. Spatial transcriptomics identified DC-LAMP+ CCR7⁺ migratory cDC1s within nucleating niches enriched in CD4⁺, CD8⁺ T cells, and B cells in mouse and human tumors. ImgTLS sustained B cell and T cell responses, and promoted systemic immunity through clonal expansion in abscopal tumors. Together, our findings establish cellular reprogramming as a strategy to engineer intratumoral lymphoid niches and overcome resistance to immunotherapy.