Necrophagy, DaNGeRous indigestion, defecation and immunity to cancer

Hosted by the School of Medicine at Cardiff University

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Like all homeostatic circuits, immunity relies on an integrated system of sensors, transducers and effectors that can be analysed in cellular or molecular terms. At the cellular level, T and B lymphocytes act as an effector arm of immunity that is mobilised in response to signals transduced by innate immune cells that detect a given insult. These innate cells are spread around the body and include dendritic cells (DCs), the chief immune sensors of pathogen invasion and tumour growth. DCs possess receptors that directly sense pathogen presence and tissue damage and that signal to control antigen presentation or to regulate a plethora of genes encoding effector proteins that regulate immunity. The lecture will focus on understanding how DCs integrate environmental signals to drive immunity to cancer, with applications in immunotherapy.

References:

1. Henry, C. M., Castellanos, C. A. & Reis e Sousa, C. DNGR-1-mediated cross-presentation of dead cell-associated antigens. Semin Immunol 66, 101726 (2023).
2. Cabeza-Cabrerizo, M., Cardoso, A., Minutti, C. M., Pereira da Costa, M. & Reis e Sousa, C. Dendritic Cells Revisited. Annu Rev Immunol 39, 131–166 (2021).
3. Cabeza-Cabrerizo, M. et al. Recruitment of dendritic cell progenitors to foci of influenza A virus infection sustains immunity. Sci Immunol 6, eabi9331 (2021).
4. Giampazolias, E. et al. Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity. Cell 184, 4016-4031.e22 (2021).
5. Canton, J. et al. The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens. Nature Immunology 22, 140–153 (2021).

Caetano Reis e Sousa is a Principal Group Leader and Assistant Research Director at the Francis Crick Institute and Head of the Immunobiology Laboratory. He is also Visiting Professor of Immunology in the Department of Medicine at Imperial College London and holds honorary professorships at both University College London and King's College London. His contributions have been widely recognised and he is included in the list of Highly Cited Researchers (2014-present) and has won the BD Biosciences Prize of the European Macrophage and Dendritic Cell Society (2002), the Liliane Bettencourt for Life Sciences Award (2008), the Award for Excellence in Basic/Translational Research from the European Society for Clinical Investigation (2011), the Louis-Jeantet Prize for Medicine (2017) and the Bial Award in Biomedicine (2019). He is co-founder of Adendra Therapeutics (2021).

He is a fellow of the Royal Society (elected 2019), fellow of The Academy of Medical Sciences (elected 2006), a member of the European Molecular Biology Organisation (EMBO; elected 2006) and was made an Officer of the Order of Sant'Iago da Espada by the government of Portugal in 2009.