OCR Event Manager - Master Calendar

Biophysics of T cells in cancer

Abstract: Effector CD8+ T cells must make cell-to-cell contacts (TCR-MHC-antigenic-peptide-complex) to identify and eliminate cancer cells selectively. This requirement could become a make-or-break factor in the clearance of solid tumors, where T cells have to actively search for the cancer cells in the tissue. Several immunotherapies, such as checkpoint blockade and adoptive T cell therapy, have been proposed; however, all of these essentially aim to make T cells better killers, not migrators. In this seminar, we recognize an equally important factor crucial for T cell success, i.e., T cell migration in tissue. T cells have been assumed to be optimal navigators based on evolutionary reasons, an idea we challenge. Our recent efforts mathematical modeling T cell migration establish that T cells migrate fast through 3D environments via a hybrid amoeboid-mesenchymal model that combines bleb-based protrusions with weak and transient adhesions to achieve high migration speeds (Alonso Matilla et al., Cell Reports, 2026). We have further found that migration speed can be increased by genetic targeting of key components underlying this mechanism, leading to the development of “physically optimized” T cells that can navigate the mechanically challenging tumor microenvironment. We find that, consistent with our model predictions, engineering T cells to express constitutively active Rho induces a strong contractile phenotype that increases cell motility and carcinoma cell engagement/killing in pancreatic tumor microenvironments. Similarly, we find that knockout of RASA2, which perturbs Ras signaling, results in faster B7-H3 CAR-T cell migration in normal murine brain tissue and better antitumoral activity against patient-derived murine models of diffuse midline glioma, a devastating pediatric brain tumor. We also applied classic collision theory developed by Smoluchowski for diffusion-limited chemical reactions to set upper bounds on T cell collisions with cancer cells. Together, these results advance our fundamental understanding of the biophysics of T cell migration, which we intend to exploit for better immunotherapies for solid tumors that are focused on making T cells both powerful killers and adept at rapidly locating target cancer cells.

Biography: David Odde is a Professor of Biomedical Engineering at the University of Minnesota. Trained as a chemical engineer at the University of Minnesota (B.Ch.E) and Rutgers University (M.S. and Ph.D.), Odde joined the newly created Department of Biomedical Engineering at the University of Minnesota in 1999 where he is a professor and Co-Director of the Therapy Modeling & Design Center. In his research, Odde’s group builds computer models of cellular and molecular self-assembly and force-generation-dissipation dynamics, and tests the models experimentally using digital microscopic imaging of living cells ex vivo and in engineered microenvironments. His group seeks to bring an engineering approach that uses physics-based modeling and analysis to understand, predict, and control disease outcomes (oddelab.umn.edu). Dr. Odde is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the Biomedical Engineering Society (BMES), the International Academy of Medical and Biological Engineering (IAMBE), and the American Association for the Advancement of Science (AAAS) and was the Director of the Physical Sciences in Oncology Center NCI U54 at the University of Minnesota (psoc.umn.edu), which was focused on modeling the mechanics of cancer cell migration in biologically relevant contexts. He is currently the PI on an NCI P01 program project grant focused on immune cell migration and the tumor microenvironment.