Willemijn H. van Deursen

All Publications

• Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity SCIENCE IMMUNOLOGY Zhang, T., Yu, W., Cheng, X., Yeung, J., Ahumada, V., Norris, P. C., Pearson, M. J., Yang, X., van Deursen, W., Halcovich, C., Nassar, A., Vesely, M. D., Zhang, Y., Zhang, J., Ji, L., Flies, D. B., Liu, L., Langermann, S., LaRochelle, W. J., Humphrey, R., Zhao, D., Zhang, Q., Zhang, J., Gu, R., Schalper, K. A., Sanmamed, M. F., Chen, L. 2024; 9 (94): eadh2334

  Abstract

  T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.

  View details for DOI 10.1126/sciimmunol.adh2334

  View details for Web of Science ID 001209051800002

  View details for PubMedID 38669316

• Screws or Sutures? A Pediatric Cadaveric Study of Tibial Spine Fracture Repairs. The American journal of sports medicine Johnstone, T. M., Baird, D. W., Cuellar-Montes, A., van Deursen, W. H., Tompkins, M., Ganley, T. J., Yen, Y. M., Ellis, H. B., Chan, C. K., Green, D. W., Sherman, S. L., Shea, K. G. 2023: 3635465231181059

  Abstract

  Tibial spine fractures are common in the pediatric population because of the biomechanical properties of children's subchondral epiphyseal bone. Most studies in porcine or adult human bone suggest that suture fixation performs better than screw fixation, but these tissues may be poor surrogates for pediatric bone. No previous study has evaluated fixation methods in human pediatric knees.To quantify the biomechanical properties of 2-screw and 2-suture repair of tibial spine fracture in human pediatric knees.Controlled laboratory study.Cadaveric specimens were randomly assigned to either 2-screw or 2-suture fixation. A standardized Meyers-Mckeever type 3 tibial spine fracture was induced. Screw-fixation fractures were reduced with two 4.0-mm cannulated screws and washers. Suture-fixation fractures were reduced by passing 2 No. 2 FiberWire sutures through the fracture fragment and the base of the anterior cruciate ligament. Sutures were secured through bony tunnels over a 1-cm tibial cortical bridge. Each specimen was mounted at 30° of flexion. A cyclic loading protocol was applied to each specimen, followed by a load-to-failure test. Outcome measures were ultimate failure load, stiffness, and fixation elongation.Twelve matched pediatric cadaveric knees were tested. Repair groups had identical mean (8.3 years) and median (8.5 years) ages and an identical number of samples of each laterality. Ultimate failure load did not significantly differ between screw (mean ± SD, 143.52 ± 41.9 7 N) and suture (135.35 ± 47.94 N) fixations (P = .760). Screws demonstrated increased stiffness and decreased elongation, although neither result was statistically significant at the .05 level (21.79 vs 13.83 N/mm and 5.02 vs 8.46 mm; P = .076 and P = .069, respectively).Screw fixation and suture fixation of tibial spine fractures in human pediatric tissue were biomechanically comparable.Suture fixations are not biomechanically superior to screw fixations in pediatric bone. Pediatric bone fails at lower loads, and in different modes, compared with adult cadaveric bone and porcine bone. Further investigation into optimal repair is warranted, including techniques that may reduce suture pullout and "cheese-wiring" through softer pediatric bone. This study provides new biomechanical data regarding the properties of different fixation types in pediatric tibial spine fractures to inform clinical management of these injuries.

  View details for DOI 10.1177/03635465231181059

  View details for PubMedID 37382335