Yonglu Che, MD

All Publications

• Induced B Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response PNAS Che, Y., Lee, J., Abou-Taleb, F., Rieger, K. E., Satpathy, A. T., Chang, A. S., Chang, H. Y. 2025: e2501269122

  Abstract

  Immune checkpoint inhibitors such as anti-Programmed Death-1 antibodies (aPD-1) can be effective in treating advanced cancers. However, many patients do not respond, and the mechanisms underlying these differences remain incompletely understood. In this study, we profile a cohort of patients with locally advanced or metastatic basal cell carcinoma undergoing aPD-1 therapy using single-cell RNA sequencing, high-definition spatial transcriptomics in tumors and draining lymph nodes, and spatial immunoreceptor profiling, with long-term clinical follow-up. We find that successful responses to PD-1 inhibition are characterized by an induction of B cell receptor (BCR) clonal diversity after treatment initiation. These induced BCR clones spatially colocalize with T cell clones, facilitate their activation, and traffic alongside them between tumor and draining lymph nodes to enhance tumor clearance. Furthermore, we validated aPD-1-induced BCR diversity as a predictor of clinical response in a larger cohort of glioblastoma, melanoma, and head and neck squamous cell carcinoma patients, suggesting that this is a generalizable predictor of treatment response across many types of cancers. We find that pretreatment tumors harbor a characteristic gene expression signature that portends a higher probability of inducing BCR clonal diversity after aPD-1 therapy, and we develop a machine learning model that predicts PD-1-induced BCR clonal diversity from baseline tumor RNA sequencing. These findings underscore a dynamic role of B cell diversity during immunotherapy, highlighting its importance as a prognostic marker and a potential target for intervention in non-responders.

  View details for DOI 10.1073/pnas.2501269122

• Patterning droplets with durotaxis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Style, R. W., Che, Y., Park, S. J., Weon, B. M., Je, J. H., Hyland, C., German, G. K., Power, M. P., Wilen, L. A., Wettlaufer, J. S., Dufresne, E. R. 2013; 110 (31): 12541-12544

  Abstract

  Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate--a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.

  View details for DOI 10.1073/pnas.1307122110

  View details for Web of Science ID 000322441500024

  View details for PubMedID 23798415

  View details for PubMedCentralID PMC3732974

• Universal Deformation of Soft Substrates Near a Contact Line and the Direct Measurement of Solid Surface Stresses PHYSICAL REVIEW LETTERS Style, R. W., Boltyanskiy, R., Che, Y., Wettlaufer, J. S., Wilen, L. A., Dufresne, E. R. 2013; 110 (6)

  Abstract

  Droplets deform soft substrates near their contact lines. Using confocal microscopy, we measure the deformation of silicone gel substrates due to glycerol and fluorinated-oil droplets for a range of droplet radii and substrate thicknesses. For all droplets, the substrate deformation takes a universal shape close to the contact line that depends on liquid composition, but is independent of droplet size and substrate thickness. This shape is determined by a balance of interfacial tensions at the contact line and provides a novel method for direct determination of the surface stresses of soft substrates. Moreover, we measure the change in contact angle with droplet radius and show that Young's law fails for small droplets when their radii approach an elastocapillary length scale. For larger droplets the macroscopic contact angle is constant, consistent with Young's law.

  View details for DOI 10.1103/PhysRevLett.110.066103

  View details for Web of Science ID 000314770600016

  View details for PubMedID 23432280

• Cadherin-based intercellular adhesions organize epithelial cell-matrix traction forces PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Mertz, A. F., Che, Y., Banerjee, S., Goldstein, J. M., Rosowski, K. A., Revilla, S. F., Niessen, C. M., Marchetti, M. C., Dufresne, E. R., Horsley, V. 2013; 110 (3): 842-847

  Abstract

  Cell-cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of cross talk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell-cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell-cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease.

  View details for DOI 10.1073/pnas.1217279110

  View details for Web of Science ID 000313909100021

  View details for PubMedID 23277553

  View details for PubMedCentralID PMC3549115

• Scaling of Traction Forces with the Size of Cohesive Cell Colonies PHYSICAL REVIEW LETTERS Mertz, A. F., Banerjee, S., Che, Y., German, G. K., Xu, Y., Hyland, C., Marchetti, M. C., Horsley, V., Dufresne, E. R. 2012; 108 (19)

  Abstract

  To understand how the mechanical properties of tissues emerge from interactions of multiple cells, we measure traction stresses of cohesive colonies of 1-27 cells adherent to soft substrates. We find that traction stresses are generally localized at the periphery of the colony and the total traction force scales with the colony radius. For large colony sizes, the scaling appears to approach linear, suggesting the emergence of an apparent surface tension of the order of 10(-3)  N/m. A simple model of the cell colony as a contractile elastic medium coupled to the substrate captures the spatial distribution of traction forces and the scaling of traction forces with the colony size.

  View details for DOI 10.1103/PhysRevLett.108.198101

  View details for Web of Science ID 000303761600023

  View details for PubMedID 23003091

  View details for PubMedCentralID PMC4098718