Effective tissue immunity depends on the coordinated action of multiple cell types, whose interactions shape whether a response is productive, tolerogenic, or pathological. Across patients and tissues, these multicellular interactions appear to converge into a finite set of recurrent organizations, which we call immune archetypes. First, I will describe how archetypes of the tumor microenvironment were defined across human solid tumors, revealing dominant immune networks that recur independently of tissue of origin. Second, I will show how these human archetypes map onto widely used mouse tumor models, uncovering conserved and coordinated gene programs across T cells and mononuclear phagocytes. Finally, I will move beyond cancer to show how we used single-cell spatial transcriptomics on FFPE tissue to extend the archetype framework to IBD, identifying networks tied to treatment response.
About the speaker
Alexis Combes is an Assistant Professor in the Department of Pathology at the University of California, San Francisco, with a joint appointment in the Division of Gastroenterology, and a faculty member of the Bakar ImmunoX Program. He trained as an immunologist and cell biologist at the Centre d'Immunologie de Marseille-Luminy, where his graduate work focused on myeloid cell biology. Since joining the UCSF faculty in 2022, he has led a hybrid experimental and computational research program centered on tissue immunity, dedicated to unraveling the interconnected cell states that drive maladaptive immune responses. His group leverages systems immunology approaches and single-cell omics, integrating multi-dimensional data with human clinical specimens and complementary mouse models. He also serves as Faculty Director of the Disease-to-Biology (D2B) CoLab, a collaborative unit supporting UCSF investigators in applying multi-parametric single-cell technologies across clinical tissues and model organisms.
