Anne will present a dynamic 3D imaging and integrated transcriptomics platform; BEHAV3D5, that has been developed to exploit immune-organoid co-cultures for understanding and improving the dynamic mode-of-action of engineered T cells in a patient personalized manner 5,6. Applied to various solid tumor types modeled with patient derived organoids and emerging T cell therapies, BEHAV3D revealed a high heterogeneity in targeting efficacy and functional behavior. Combined with a module of Behavior-guided sc transcriptomics, they could identify the gene signature of the most potent ‘serial killer’ T cells as well define combinatorial treatment to prime immunotherapy-mediating killing. Thus, BEHAV3D holds promise for improving dynamic solid tumor-targeting of T cell immunotherapies at patient population scale.
Over the years Dr Rios’ research interests have focussed on advancing 3D imaging technologies to explore developmental processes1, stem cell biology2 and cancer progression3. As tenured group leader and head of the imaging center at the Princess Máxima Center for pediatric oncology and principal investigator of the Oncode cancer institute of excellence in the Netherlands, her research direction has now centered towards understanding and improving cancer immunotherapies. She leads an interdisciplinary team with a strong emphasis on technological advancements, combining organoid technology, tissue imaging4, and vision-based multi-omics5 to identify new therapeutic targets and factors that influence treatment outcomes for pediatric tumors and breast cancer.
1. Rios, A. C., Serralbo, O., Salgado, D. & Marcelle, C. Neural crest regulates myogenesis through the transient activation of NOTCH. Nature 473, 532–535 (2011).
2. Rios, A. C., Fu, N. Y., Lindeman, G. J. & Visvader, J. E. In situ identification of bipotent stem cells in the mammary gland. Nature 506, 322–327 (2014).
3. Rios, A. C. et al. Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging. Cancer Cell 35, 618-632.e6 (2019).
4. Ineveld, R. L. van et al. Revealing the spatio-phenotypic patterning of cells in healthy and tumor tissues with mLSR-3D and STAPL-3D. Nat Biotechnol 39, 1239–1245 (2021).
5. Dekkers, J. F. et al. Uncovering the mode of action of engineered T cells in patient cancer organoids. Nat Biotechnol 1–10 (2022)
6. Alieva, M., Wezenaar, A. K. L., Wehrens, E. J. & Rios, A. C. Bridging live-cell imaging and next-generation cancer treatment. Nat. Rev. Cancer 1–15 (2023)