Constitutive PSGL-1 Correlates with CD30 and TCR Pathways and Represents a Potential Target for Immunotherapy in Anaplastic Large T-Cell Lymphoma

  • Cancers (Basel). 2021 Jun 12;13(12):2958. doi: 10.3390/cancers13122958.
Beatrice Belmonte  1 ,  Valeria Cancila  1 ,  Alessandro Gulino  1 ,  Mohsen Navari  2  3  4 ,  Walter Arancio  5 ,  Paolo Macor  6 ,  Andrea Balduit  6 ,  Sara Capolla  6 ,  Gaia Morello  1 ,  Davide Vacca  1 ,  Ines Ferrara  1 ,  Giorgio Bertolazzi  1 ,  Carmela Rita Balistreri  7 ,  Paolo Amico  8 ,  Federica Ferrante  1 ,  Antonino Maiorana  9 ,  Tiziana Salviato  9 ,  Pier Paolo Piccaluga  10  11  12 ,  Alessandro Mangogna  13
Affiliations
  • 1. Tumor Immunology Unit, Department of Health Sciences, University of Palermo, 90134 Palermo, Italy.
  • 2. Department of Medical Biotechnology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh 95196 33787, Iran.
  • 3. Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh 95196 33787, Iran.
  • 4. Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad 91766 99199, Iran.
  • 5. Advanced Data Analysis Group, Fondazione Ri.MED, 90133 Palermo, Italy.
  • 6. Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
  • 7. Department of BioMedicine, Neuroscience, and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90134 Palermo, Italy.
  • 8. Department of Pathology, Cannizzaro Hospital, 95126 Catania, Italy.
  • 9. Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia, 41121 Modena, Italy.
  • 10. Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.
  • 11. Section of Genomics and Personalized Medicine, Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST), 90139 Palermo, Italy.
  • 12. Department of Pathology, School of Medicine, Jomo Kenyatta University of Agriculture and Technology, 00622 Juja, Kenya.
  • 13. Institute for Maternal and Child Health, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) "Burlo Garofolo", 34137 Trieste, Italy.
PMID: 34204843 DOI: 10.3390/cancers13122958
Abstract

Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoproliferative disorders and in Multiple Myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T- and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (Lck, LAT, Syk and JUN), suggesting that the common dysregulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the Complement System and induction of Apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs.

Keywords
ALCL; ALK; CD30; PSGL-1; PTCL; TCR; immunotherapy.