(2021) Constitutive psgl-1 correlates with cd30 and tcr pathways and represents a potential target for immunotherapy in anaplastic large t-cell lymphoma. Cancers. ISSN 20726694 (ISSN)
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Abstract
Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoprolif-erative 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 dysreg-ulation 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Item Type: | Article |
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Keywords: | PSGL-1; PTCL; ALCL; ALK; CD30; TCR; immunotherapy |
Journal or Publication Title: | Cancers |
Volume: | 13 |
Number: | 12 |
Identification Number: | https://doi.org/10.3390/cancers13122958 |
ISSN: | 20726694 (ISSN) |
Depositing User: | پریسا مرادی |
URI: | http://eprints.thums.ac.ir/id/eprint/3347 |
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