E-Cadherin Expression and Blunted Interferon Response in Blastic Plasmacytoid Dendritic Cell Neoplasm

Lorenzi, Luisa; Lonardi, Silvia; Vairo, Donatella; Bernardelli, Andrea; Tomaselli, Michela; Bugatti, Mattia; Licini, Sara; Arisi, Mariachiara; Cerroni, Lorenzo; Tucci, Alessandra; Vermi, William; Giliani, Silvia; Facchetti, Fabio

doi:10.1097/pas.0000000000001747

Cited by 5 publications

(5 citation statements)

References 64 publications

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“…The extent of staining, defined as the percentage of positively stained cells, was scored as 1 (≤10%), 2 (11−50%), 3 (51−80%) and 4 (>80%). The total immunoreactive score (IRS) was obtained by multiplying the staining intensity score and the staining extent score and ranked from 0 to 12 ( 22 , 23 ). The evaluation of staining intensity was carried out by two pathologists independently, who were kept blinded to the associated clinical data.…”

Section: Methodsmentioning

confidence: 99%

GLIPR2: a potential biomarker and therapeutic target unveiled – Insights from extensive pan-cancer analyses, with a spotlight on lung adenocarcinoma

Lin,

Zhang,

et al. 2024

Front. Immunol.

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BackgroundGlioma pathogenesis related-2 (GLIPR2), an emerging Golgi membrane protein implicated in autophagy, has received limited attention in current scholarly discourse.MethodsLeveraging extensive datasets, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we conducted a comprehensive investigation into GLIPR2 expression across diverse human malignancies. Utilizing UALCAN, OncoDB, MEXPRESS and cBioPortal databases, we scrutinized GLIPR2 mutation patterns and methylation landscapes. The integration of bulk and single-cell RNA sequencing facilitated elucidation of relationships among cellular heterogeneity, immune infiltration, and GLIPR2 levels in pan-cancer. Employing ROC and KM analyses, we unveiled the diagnostic and prognostic potential of GLIPR2 across diverse cancers. Immunohistochemistry provided insights into GLIPR2 expression patterns in a multicenter cohort spanning various cancer types. In vitro functional experiments, including transwell assays, wound healing analyses, and drug sensitivity testing, were employed to delineate the tumor suppressive role of GLIPR2.ResultsGLIPR2 expression was significantly reduced in neoplastic tissues compared to its prevalence in healthy tissues. Copy number variations (CNV) and alterations in methylation patterns exhibited discernible correlations with GLIPR2 expression within tumor tissues. Moreover, GLIPR2 demonstrated diagnostic and prognostic implications, showing pronounced associations with the expression profiles of numerous immune checkpoint genes and the relative abundance of immune cells in the neoplastic microenvironment. This multifaceted influence was evident across various cancer types, with lung adenocarcinoma (LUAD) being particularly prominent. Notably, patients with LUAD exhibited a significant decrease in GLIPR2 expression within practical clinical settings. Elevated GLIPR2 expression correlated with improved prognostic outcomes specifically in LUAD. Following radiotherapy, LUAD cases displayed an increased presence of GLIPR2+ infiltrating cellular constituents, indicating a notable correlation with heightened sensitivity to radiation-induced therapeutic modalities. A battery of experiments validated the functional role of GLIPR2 in suppressing the malignant phenotype and enhancing treatment sensitivity.ConclusionIn pan-cancer, particularly in LUAD, GLIPR2 emerges as a promising novel biomarker and tumor suppressor. Its involvement in immune cell infiltration suggests potential as an immunotherapeutic target.

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Section: Methodsmentioning

confidence: 99%

GLIPR2: a potential biomarker and therapeutic target unveiled – Insights from extensive pan-cancer analyses, with a spotlight on lung adenocarcinoma

Lin,

Zhang,

et al. 2024

Front. Immunol.

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“…To this end, the blastic pDC neoplasm is an aggressive neoplasm, which frequently responds to venetoclax 11 . A majority of these tumours seems to lack expression pf PD-L1/CD274 65 , suggesting that at least some of them belong to the P3-pDC subpopulation characterized as PD-L1 -CD80 + 12 , Fig. 1.…”

Section: Future Perspectives: Can Pdcs Be Targeted As a Novel Treatme...mentioning

confidence: 98%

The Yin and Yang of Plasmacytoid Dendritic Cells – SARS-CoV-2 Protection versus Susceptibility to Selected Autoimmune Diseases

Smith

2023

MRAJ

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Dendritic cells can be subdivided into three major subsets. The conventional (classical) dendritic cells (cDCs), also known as myeloid DCs, can be further split into the cDC1 and cDC2 subpopulations. The third subpopulation is the plasmacytoid DC (pDC). The pDCs are unique because they constitute the leukocyte, which secretes the largest amount of interferon (IFN). Since IFNs are crucial in the defence against viruses, it could be hypothesized that reduced IFN production by pDCs could cause susceptibility to viral infections in general. However, this does not seem to be the case, since it was not until the SARS-CoV-2 pandemic that the essential role of pDCs in viral immunity was revealed. In this review we discuss the role of pDCs in the protection against Covid-19 and the mechanisms underlying susceptibility when these cells are malfunctioning as seen in haematological malignancies. In contrast, overactive pDCs can lead to selected autoimmune diseases, where systemic lupus (SLE) is the premier example, demonstrating the yin and yang relationship.

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“…However, it should be noted that in reactive lymph nodes and cutaneous lupus erythematosus most pDCs lack PD-L1 (Fig. 3 ) as well as E2-2/TCF4 + BPDCN neoplastic cells [ 85 ].…”

Section: Introductionmentioning

confidence: 99%

Plasmacytoid dendritic cells at the forefront of anti-cancer immunity: rewiring strategies for tumor microenvironment remodeling

Monti,

Ferrari,

Gazzurelli

et al. 2024

J Exp Clin Cancer Res

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Plasmacytoid dendritic cells (pDCs) are multifaceted immune cells executing various innate immunological functions. Their first line of defence consists in type I interferons (I-IFN) production upon nucleic acids sensing through endosomal Toll-like receptor (TLR) 7- and 9-dependent signalling pathways. Type I IFNs are a class of proinflammatory cytokines that have context-dependent functions on cancer immunosurveillance and immunoediting. In the last few years, different studies have reported that pDCs are also able to sense cytosolic DNA through cGAS–STING (stimulator of interferon genes) pathway eliciting a potent I-IFN production independently of TLR7/9. Human pDCs are also endowed with direct effector functions via the upregulation of TRAIL and production of granzyme B, the latter modulated by cytokines abundant in cancer tissues. pDCs have been detected in a wide variety of human malignant neoplasms, including virus-associated cancers, recruited by chemotactic stimuli. Although the role of pDCs in cancer immune surveillance is still uncompletely understood, their spontaneous activation has been rarely documented; moreover, their presence in the tumor microenvironment (TME) has been associated with a tolerogenic phenotype induced by immunosuppressive cytokines or oncometabolites. Currently tested treatment options can lead to pDCs activation and disruption of the immunosuppressive TME, providing a relevant clinical benefit. On the contrary, the antibody–drug conjugates targeting BDCA-2 on immunosuppressive tumor-associated pDCs (TA-pDCs) could be proposed as novel immunomodulatory therapies to achieve disease control in patients with advance stage hematologic malignancies or solid tumors. This Review integrate recent evidence on the biology of pDCs and their pharmacological modulation, suggesting their relevant role at the forefront of cancer immunity.

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E-Cadherin Expression and Blunted Interferon Response in Blastic Plasmacytoid Dendritic Cell Neoplasm

Abstract: Supplemental Digital Content is available in the text.

Cited by 5 publications

References 64 publications

GLIPR2: a potential biomarker and therapeutic target unveiled – Insights from extensive pan-cancer analyses, with a spotlight on lung adenocarcinoma

GLIPR2: a potential biomarker and therapeutic target unveiled – Insights from extensive pan-cancer analyses, with a spotlight on lung adenocarcinoma

The Yin and Yang of Plasmacytoid Dendritic Cells – SARS-CoV-2 Protection versus Susceptibility to Selected Autoimmune Diseases

Plasmacytoid dendritic cells at the forefront of anti-cancer immunity: rewiring strategies for tumor microenvironment remodeling

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