William Lee Wang

All Publications

• The CCR6-CCL20 axis promotes regulatory T cell glycolysis and immunosuppression in tumors. Cancer immunology research Pant, A., Jain, A., Chen, Y., Patel, K., Saleh, L., Tzeng, S., Nitta, R. T., Zhao, L., Wu, C. Y., Bederson, M., Wang, W. L., Bergsneider, B. H., Choi, J., Medikonda, R., Verma, R., Cho, K. B., Kim, L. H., Kim, J. E., Yazigi, E., Lee, S. Y., Rajendran, S., Rajappa, P., Mackall, C. L., Li, G., Tyler, B., Brem, H., Pardoll, D. M., Lim, M., Jackson, C. M. 2024

  Abstract

  Regulatory T cells (Tregs) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity towards CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wildtype mice, and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.

  View details for DOI 10.1158/2326-6066.CIR-24-0230

  View details for PubMedID 39133127

• Lisocabtagene maraleucel for treatment of relapsed and refractory primary mediastinal large B-cell lymphoma in an adolescent patient. EJHaem Lee, D., Goyal, A., Wang, W. L., Ananth, S., Lau, E., Binkley, M. S., Bharadwaj, S., Dahiya, S. 2024; 5 (1): 153-156

  Abstract

  The safety and efficacy of CAR T-cell therapy are unknown in pediatric and adolescent patients with relapsed or refractory primary mediastinal large B-cell lymphoma (R/R PMBCL) which is associated with dismal prognosis. Here, we present a case report of a 16-year-old patient with R/R PMBCL treated with lisocabtagene maraleucel including correlative studies. Patient achieved complete response at 6 months without cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. She only experienced mild cytopenias, requiring filgrastim once. This report highlights the safety and efficacy of lisocabtagene maraleucel in this population, warranting prospective studies to improve clinical outcomes.

  View details for DOI 10.1002/jha2.859

  View details for PubMedID 38406546

• Geometric deep learning enables 3D kinematic profiling across species and environments. Nature methods Dunn, T. W., Marshall, J. D., Severson, K. S., Aldarondo, D. E., Hildebrand, D. G., Chettih, S. N., Wang, W. L., Gellis, A. J., Carlson, D. E., Aronov, D., Freiwald, W. A., Wang, F., Ölveczky, B. P. 2021; 18 (5): 564-573

  Abstract

  Comprehensive descriptions of animal behavior require precise three-dimensional (3D) measurements of whole-body movements. Although two-dimensional approaches can track visible landmarks in restrictive environments, performance drops in freely moving animals, due to occlusions and appearance changes. Therefore, we designed DANNCE to robustly track anatomical landmarks in 3D across species and behaviors. DANNCE uses projective geometry to construct inputs to a convolutional neural network that leverages learned 3D geometric reasoning. We trained and benchmarked DANNCE using a dataset of nearly seven million frames that relates color videos and rodent 3D poses. In rats and mice, DANNCE robustly tracked dozens of landmarks on the head, trunk, and limbs of freely moving animals in naturalistic settings. We extended DANNCE to datasets from rat pups, marmosets, and chickadees, and demonstrate quantitative profiling of behavioral lineage during development.

  View details for DOI 10.1038/s41592-021-01106-6

  View details for PubMedID 33875887

  View details for PubMedCentralID PMC8530226

• Continuous Whole-Body 3D Kinematic Recordings across the Rodent Behavioral Repertoire. Neuron Marshall, J. D., Aldarondo, D. E., Dunn, T. W., Wang, W. L., Berman, G. J., Ölveczky, B. P. 2021; 109 (3): 420-437.e8

  Abstract

  In mammalian animal models, high-resolution kinematic tracking is restricted to brief sessions in constrained environments, limiting our ability to probe naturalistic behaviors and their neural underpinnings. To address this, we developed CAPTURE (Continuous Appendicular and Postural Tracking Using Retroreflector Embedding), a behavioral monitoring system that combines motion capture and deep learning to continuously track the 3D kinematics of a rat's head, trunk, and limbs for week-long timescales in freely behaving animals. CAPTURE realizes 10- to 100-fold gains in precision and robustness compared with existing convolutional network approaches to behavioral tracking. We demonstrate CAPTURE's ability to comprehensively profile the kinematics and sequential organization of natural rodent behavior, its variation across individuals, and its perturbation by drugs and disease, including identifying perseverative grooming states in a rat model of fragile X syndrome. CAPTURE significantly expands the range of behaviors and contexts that can be quantitatively investigated, opening the door to a new understanding of natural behavior and its neural basis.

  View details for DOI 10.1016/j.neuron.2020.11.016

  View details for PubMedID 33340448

  View details for PubMedCentralID PMC7864892