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

Belmonte, Beatrice; Cancila, Valeria; Gulino, Alessandro; Navari, Mohsen; Arancio, Walter; Macor, Paolo; Balduit, Andrea; Capolla, Sara; Morello, Gaia; Vacca, Davide; Ferrara, Ines; Bertolazzi, Giorgio; Balistreri, Carmela Rita; Amico, Paolo; Ferrante, F.; Maiorana, Antonino; Salviato, Tiziana; Piccaluga, Pier Paolo; Mangogna, Alessandro

doi:10.3390/cancers13122958

Cited by 4 publications

(12 citation statements)

References 46 publications

(57 reference statements)

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“…Antibodies against the PSGL-1 or CLA glycoproteins appear to be both effective against CTCL. However, PSGL-1 is expressed by several myeloid and lymphoid malignancies such as acute myeloid leukemia, multiple myeloma, primary effusion lymphoma and ALCL, 16,17,20,36 while CLA expression was observed in a single lymphoblastoid mantle cell lymphoma presenting skin lesions. 53 The more widespread PSGL-1 expression than CLA expression and our finding that the PL1 mAb could kill CTCL, ALCL and DLBCL cell lines suggest that anti-PSGL-1 therapy might be broadened to a wider range of malignancies than anti-CLA therapy.…”

Section: Discussionmentioning

confidence: 99%

“…38 In anaplastic large cell lymphoma (ALCL), PSGL-1 was found to be highly expressed and correlated with CD30 and TCR signaling genes and was put forward as a potential therapeutic target. 20 Finally, in lymphoma mouse models PSGL-1 expression was found to promote lymphoma development and dissemination to distant organs. Taking into consideration these findings, we sought to assess whether PSGL-1 could be a therapeutic target in lymphoma.…”

mentioning

confidence: 98%

“…12 P-selectin glycoprotein ligand 1 (PSGL-1), encoded by the SELPLG gene, is a major ligand of P-, E-and L-selectin, not only widely expressed in normal lymphoid and myeloid cells but also expressed in hematological malignancies. [13][14][15][16][17][18][19][20][21] PSGL-1 is normally involved in cell trafficking, rolling and tethering to blood vessels, as well as homing to secondary lymphoid organs and recruitment to inflammatory sites. 14,[22][23][24][25][26][27][28][29] Recently, PSGL-1 has been shown to bind to VISTA protein under acidic conditions, typical of tumor microenvironments.…”

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confidence: 99%

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Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Pereira,

Ferreira,

dos Santos

2024

Hematological Oncology

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Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P‐selectin glycoprotein ligand 1 (PSGL‐1) is expressed at the surface of hematological malignant cells and has been shown to have a pro‐oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL‐1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL‐1 was expressed in both T and B cell‐derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell‐derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL‐1 N‐terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro‐apoptotic activity was shown to be dose‐dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti‐PSGL‐1 treatment of mice xenografted with the HUT‐78 cutaneous T‐cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti‐PSGL‐1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti‐PSGL‐1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL‐1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL‐1 as a potential target for lymphoma therapy.

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Section: Discussionmentioning

confidence: 99%

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confidence: 98%

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confidence: 99%

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Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Pereira,

Ferreira,

dos Santos

2024

Hematological Oncology

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“…It has been documented that the copy number of SELPLG was reported as a biomarker to differentiate subtypes of AML [ 29 ]. SELPLG was also identified in HNSCC and ALCL as predictor or potential therapeutic target [ 18 , 19 ]. We have firstly reported SELPLG as a prognostic biomarker for OS, which might serve as a reference factor for OS prognosis prediction in the future.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported to mediate the development and chemotherapy resistance of acute myeloid leukemia (AML), and blocking the binding of SELPLG to E-selectin is probably a new target [ 16 ]. Moreover, SELPLG has been studied in several kinds of cancers as potential diagnostic or prognostic biomarkers, such as colorectal cancer (CRC) [ 17 ], head and neck squamous cell carcinoma (HNSCC) [ 18 ], anaplastic large T-cell lymphoma (ALCL) [ 19 ], uveal melanoma [ 20 ], and so on. In The Human Protein Atlas database ( https://www.proteinatlas.org/ ), SELPLG is a favorable factor in most recorded tumors (such as cervical cancer, thyroid cancer, and so on).…”

Section: Introductionmentioning

confidence: 99%

SELPLG Expression Was Potentially Correlated With Metastasis and Prognosis of Osteosarcoma

Wang¹,

Sun²

2022

Pathol. Oncol. Res.

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Background: Osteosarcoma (OS) is the most prevalent malignant primary bone tumor in children. Selectin P ligand gene (SELPLG) has been studied in several cancers. Our research aimed to explore the role of SELPLG in OS.Methods: All OS patient data was obtained from TARGET and GEO databases. Differential expression analyses were conducted in limma package of R. Functional analyses included GO and KEGG enrichment analyses. Immune cell infiltration analysis was done in CIBERSORT software. The overall survival was calculated using survival and survminer package of R.Results: Significantly lower SELPLG expression was observed in metastatic OS samples compared with non-metastatic OS samples, both in TARGET and in GSE21257. Low SELPLG expression was an independent undesirable prognostic factor for OS patients, in both TARGET and GEO datasets. Totally 62 differentially expressed gene (DEG) overlaps were found between high SELPLG vs. low SELPLG and non-metastatic vs. metastatic OS samples, affecting metastases and thereby influencing the prognosis, which were significantly enriched in 40 GO and six KEGG terms. Five types of immune cells were significantly differentially infiltrated between high and low SELPLG expression OS patients.Conclusion: SELPLG is closely correlated with metastases and prognosis of OS patients. The OS patients with low SELPLG expression have relatively poorer prognosis and SELPLG is a potential prognostic biomarker for OS.

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Monocytic myeloid-derived suppressive cells mitigate over-adipogenesis of bone marrow microenvironment in aplastic anemia by inhibiting CD8+ T cells

et al. 2022

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Aplastic anemia (AA) is a blood disorder resulted from over-activated T-cell related hematopoietic failure, with the characterization of hypocellularity and enhanced adipogenic differentiation of mesenchymal stroma cells (MSCs) in bone marrow (BM). However, little is known about the relationship between immune imbalance and polarized adipogenic abnormity of BM microenvironment in this disease entity. In the present study, we differentiated BM-MSCs into osteoblastic or adipogenic lineages to mimic the osteo-adipogenic differentiation. Activated CD8+ T cells and interferon-γ (IFN-γ) were found to stimulate adipogenesis of BM-MSCs either in vitro or in vivo of AA mouse model. Interestingly, myeloid-derived suppressive cells (MDSCs), one of the immune-regulating populations, were decreased within BM of AA mice. We found that it was not CD11b+Ly6G+Ly6C- granulocytic-MDSCs (gMDSCs) but CD11b+Ly6G-Ly6C+ monocytic-MDSCs (mMDSCs) inhibiting both T cell proliferation and IFN-γ production via inducible nitric oxide synthetase (iNOS) pathway. Single-cell RNA-sequencing (scRNA-seq) of AA- and mMDSCs-treated murine BM cells revealed that mMDSCs transfusion could reconstitute BM hematopoietic progenitors by inhibiting T cells population and signature cytokines and decreasing immature Adipo-Cxcl12-abundant reticular cells within BM. Multi-injection of mMDSCs into AA mice reduced intra-BM T cells infiltration and suppressed BM adipogenesis, which subsequently restored the intra-BM immune balance and eventually prevented pancytopenia and hypo-hematopoiesis. In conclusion, adoptive transfusion of mMDSCs might be a novel immune-regulating strategy to treat AA, accounting for not only restoring the intra-BM immune balance but also improving stroma’s multi-differentiating microenvironment.

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

Cited by 4 publications

References 46 publications

Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

Antibody targeting of surface P‐selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition

SELPLG Expression Was Potentially Correlated With Metastasis and Prognosis of Osteosarcoma

Monocytic myeloid-derived suppressive cells mitigate over-adipogenesis of bone marrow microenvironment in aplastic anemia by inhibiting CD8+ T cells

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