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Article ; Online: Targeting tumour-reprogrammed myeloid cells: the new battleground in cancer immunotherapy.

De Sanctis, Francesco / Adamo, Annalisa / Canè, Stefania / Ugel, Stefano

2022 Volume 45, Issue 2, Page(s) 163–186

Abstract: Tumour microenvironment is a complex ecosystem in which myeloid cells are the most abundant immune elements. This cell compartment is composed by different cell types, including neutrophils, macrophages, dendritic cells, and monocytes but also unexpected ...

Abstract	Tumour microenvironment is a complex ecosystem in which myeloid cells are the most abundant immune elements. This cell compartment is composed by different cell types, including neutrophils, macrophages, dendritic cells, and monocytes but also unexpected cell populations with immunosuppressive and pro-tumour roles. Indeed, the release of tumour-derived factors influences physiological haematopoiesis producing unconventional cells with immunosuppressive and tolerogenic functions such as myeloid-derived suppressor cells. These pro-tumour myeloid cell populations not only support immune escape directly but also assist tumour invasion trough non-immunological activities. It is therefore not surprising that these cell subsets considerably impact in tumour progression and cancer therapy resistance, including immunotherapy, and are being investigated as potential targets for developing a new era of cancer therapy. In this review, we discuss emerging strategies able to modulate the functional activity of these tumour-supporting myeloid cells subverting their accumulation, recruitment, survival, and functions. These innovative approaches will help develop innovative, or improve existing, cancer treatments.
MeSH term(s)	Humans ; Ecosystem ; Myeloid Cells ; Neoplasms ; Immunotherapy ; Macrophages ; Myeloid-Derived Suppressor Cells ; Tumor Microenvironment
Language	English
Publishing date	2022-09-26
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-022-00965-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1425: Show issues

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Book: Triest

Adamo, Annalisa

Zwischen Karst und Meer

2015

Author's details	Annalisa Adamo
Language	German
Size	176 S, 205 mm x 145 mm
Edition	1. Aufl
Publisher	Styria Regional
Publishing place	Graz
Document type	Book
ISBN	370120196X ; 9783701201969
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Moonlighting Proteins Are Important Players in Cancer Immunology.

Adamo, Annalisa / Frusteri, Cristina / Pallotta, Maria Teresa / Pirali, Tracey / Sartoris, Silvia / Ugel, Stefano

Frontiers in immunology

2021 Volume 11, Page(s) 613069

Abstract: Plasticity and adaptation to environmental stress are the main features that tumor and immune system share. Except for intrinsic and high-defined properties, cancer and immune cells need to overcome the opponent's defenses by activating more effective ... ...

Abstract	Plasticity and adaptation to environmental stress are the main features that tumor and immune system share. Except for intrinsic and high-defined properties, cancer and immune cells need to overcome the opponent's defenses by activating more effective signaling networks, based on common elements such as transcriptional factors, protein-based complexes and receptors. Interestingly, growing evidence point to an increasing number of proteins capable of performing diverse and unpredictable functions. These multifunctional proteins are defined as moonlighting proteins. During cancer progression, several moonlighting proteins are involved in promoting an immunosuppressive microenvironment by reprogramming immune cells to support tumor growth and metastatic spread. Conversely, other moonlighting proteins support tumor antigen presentation and lymphocytes activation, leading to several anti-cancer immunological responses. In this light, moonlighting proteins could be used as promising new potential targets for improving current cancer therapies. In this review, we describe in details 12 unprecedented moonlighting proteins that during cancer progression play a decisive role in guiding cancer-associated immunomodulation by shaping innate or adaptive immune response.
MeSH term(s)	Animals ; Cell Proliferation/physiology ; Humans ; Immunity/immunology ; Immunomodulation/immunology ; Lymphocyte Activation/immunology ; Neoplasms/immunology ; Proteins/immunology
Chemical Substances	Proteins
Language	English
Publishing date	2021-01-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.613069
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: B-cell receptor signaling activity identifies patients with mantle cell lymphoma at higher risk of progression.

Gambino, Simona / Quaglia, Francesca Maria / Galasso, Marilisa / Cavallini, Chiara / Chignola, Roberto / Lovato, Ornella / Giacobazzi, Luca / Caligola, Simone / Adamo, Annalisa / Putta, Santosh / Aparo, Antonino / Ferrarini, Isacco / Ugel, Stefano / Giugno, Rosalba / Donadelli, Massimo / Dando, Ilaria / Krampera, Mauro / Visco, Carlo / Scupoli, Maria Teresa

Scientific reports

2024 Volume 14, Issue 1, Page(s) 6595

Abstract: Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell ... ...

Abstract	Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.
MeSH term(s)	Humans ; Adult ; Lymphoma, Mantle-Cell/pathology ; STAT5 Transcription Factor/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Receptors, Antigen, B-Cell/metabolism
Chemical Substances	STAT5 Transcription Factor ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55728-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: High-throughput analysis and functional interpretation of extracellular vesicle content in hematological malignancies

Tanasi, Ilaria / Adamo, Annalisa / Kamga, Paul Takam / Bazzoni, Riccardo / Krampera, Mauro

Computational and Structural Biotechnology Journal. 2020, v. 18

2020

Abstract: Extracellular vesicles (EVs) are membrane-coated particles secreted by virtually all cell types in response to different stimuli, both in physiological and pathological conditions. Their content generally reflects their biological functions and includes ... ...

Abstract	Extracellular vesicles (EVs) are membrane-coated particles secreted by virtually all cell types in response to different stimuli, both in physiological and pathological conditions. Their content generally reflects their biological functions and includes a variety of molecules, such as nucleic acids, proteins and cellular components. The role of EVs as signaling vehicles has been widely demonstrated. In particular, they are actively involved in the pathogenesis of several hematological malignancies (HM), mainly interacting with a number of target cells and inducing functional and epigenetic changes. In this regard, by releasing their cargo, EVs play a pivotal role in the bilateral cross-talk between tumor microenvironment and cancer cells, thus facilitating mechanisms of immune escape and supporting tumor growth and progression. Recent advances in high-throughput technologies have allowed the deep characterization and functional interpretation of EV content. In this review, the current knowledge on the high-throughput technology-based characterization of EV cargo in HM is summarized.
Keywords	biotechnology ; epigenetics ; neoplasms ; pathogenesis
Language	English
Size	p. 2670-2677.
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2020.09.027
Database	NAL-Catalogue (AGRICOLA)

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Article: High-throughput analysis and functional interpretation of extracellular vesicle content in hematological malignancies.

Tanasi, Ilaria / Adamo, Annalisa / Kamga, Paul Takam / Bazzoni, Riccardo / Krampera, Mauro

Computational and structural biotechnology journal

2020 Volume 18, Page(s) 2670–2677

Abstract: Extracellular vesicles (EVs) are membrane-coated particles secreted by virtually all cell types in response to different stimuli, both in physiological and pathological ... ...

Abstract	Extracellular vesicles (EVs) are membrane-coated particles secreted by virtually all cell types in response to different stimuli, both in physiological and pathological conditions
Language	English
Publishing date	2020-09-24
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2020.09.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Beneficial Effect of Phenytoin and Carbamazepine on

Bachetti, Tiziana / Zanni, Eleonora Di / Adamo, Annalisa / Rosamilia, Francesca / Sechi, M Margherita / Solla, Paolo / Bozzo, Matteo / Ceccherini, Isabella / Sechi, GianPietro

Frontiers in pharmacology

2021 Volume 12, Page(s) 723218

Abstract: Alexander's disease (AxD) is a rare, usually relentlessly progressive disorder of astroglial cells in the central nervous system related to mutations in the gene encoding the type III intermediate filament protein, glial fibrillary acidic protein (GFAP). ...

Abstract	Alexander's disease (AxD) is a rare, usually relentlessly progressive disorder of astroglial cells in the central nervous system related to mutations in the gene encoding the type III intermediate filament protein, glial fibrillary acidic protein (GFAP). The pathophysiology of AxD is only partially understood. Available data indicate that an excessive GFAP gene expression may play a role. In particular, a "threshold hypothesis" has been reported, suggesting that mutant GFAP representing about 20% of the total cellular GFAP should be sufficient to cause disease. Thus, strategies based on reducing cellular mutant GFAP protein levels and/or activating biological processes involved in the correct protein folding could be effective in counteracting the toxic effect of misfolded GFAP. Considering that clomipramine (CLM), which has been selected by a wide small molecules screening as the greatest inhibitory potential drug against GFAP expression, is contraindicated because of its proconvulsant activity in the infantile form of AxD, which is also characterized by the occurrence of epileptic seizures, two powerful antiepileptic agents, carbamazepine (CBZ) and phenytoin (PHT), which share specific stereochemical features in common with CLM, were taken into consideration in a reliable
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.723218
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Axon guidance cue SEMA3A promotes the aggressive phenotype of basal-like PDAC.

Lupo, Francesca / Pezzini, Francesco / Pasini, Davide / Fiorini, Elena / Adamo, Annalisa / Veghini, Lisa / Bevere, Michele / Frusteri, Cristina / Delfino, Pietro / D'agosto, Sabrina / Andreani, Silvia / Piro, Geny / Malinova, Antonia / Wang, Tian / De Sanctis, Francesco / Lawlor, Rita Teresa / Hwang, Chang-Il / Carbone, Carmine / Amelio, Ivano /

Bailey, Peter / Bronte, Vincenzo / Tuveson, David / Scarpa, Aldo / Ugel, Stefano / Corbo, Vincenzo

Gut

2024

Abstract: Objective: The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in ... ...

Abstract	Objective: The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression. Design: We integrated bulk and single-cell transcriptomic datasets of human PDAC with in situ hybridisation analyses of patients' tissues to evaluate SEMA3A expression in molecular subtypes of PDAC. Gain and loss of function experiments in PDAC cell lines and organoids were performed to dissect how SEMA3A contributes to define a biologically aggressive phenotype. Results: In PDAC tissues, SEMA3A is expressed by stromal elements and selectively enriched in basal-like/squamous epithelial cells. Accordingly, expression of SEMA3A in PDAC cells is induced by both cell-intrinsic and cell-extrinsic determinants of the basal-like phenotype. Conclusions: Here, we show that SEMA3A is a stress-sensitive locus that promotes the malignant phenotype of basal-like PDAC through both cell-intrinsic and cell-extrinsic mechanisms.
Language	English
Publishing date	2024-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2023-329807
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Zs.A 160: Show issues

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Article ; Online: Neutralization of NET-associated human ARG1 enhances cancer immunotherapy.

Science translational medicine

2023 Volume 15, Issue 687, Page(s) eabq6221

Abstract: Myeloid cells can restrain antitumor immunity by metabolic pathways, such as the degradation of l-arginine, whose concentrations are regulated by the arginase 1 (ARG1) enzyme. Results from preclinical studies indicate the important role of arginine ... ...

Abstract	Myeloid cells can restrain antitumor immunity by metabolic pathways, such as the degradation of l-arginine, whose concentrations are regulated by the arginase 1 (ARG1) enzyme. Results from preclinical studies indicate the important role of arginine metabolism in pancreatic ductal adenocarcinoma (PDAC) progression, suggesting a potential for clinical application; however, divergent evolution in ARG1 expression and function in rodents and humans has restricted clinical translation. To overcome this dichotomy, here, we show that neutrophil extracellular traps (NETs), released by spontaneously activated neutrophils isolated from patients with PDAC, create a microdomain where cathepsin S (CTSS) cleaves human (h)ARG1 into different molecular forms endowed with enhanced enzymatic activity at physiological pH. NET-associated hARG1 suppresses T lymphocytes whose proliferation is restored by either adding a hARG1-specific monoclonal antibody (mAb) or preventing CTSS-mediated cleavage, whereas small-molecule inhibitors are not effective. We show that ARG1 blockade, combined with immune checkpoint inhibitors, can restore CD8
MeSH term(s)	Humans ; Animals ; Mice ; CD8-Positive T-Lymphocytes ; Extracellular Traps/metabolism ; Arginase/metabolism ; Immunotherapy ; Pancreatic Neoplasms/therapy ; Antibodies, Monoclonal/pharmacology ; Tumor Microenvironment ; Pancreatic Neoplasms
Chemical Substances	Arginase (EC 3.5.3.1) ; Antibodies, Monoclonal ; Arg1 protein, mouse (EC 3.5.3.1)
Language	English
Publishing date	2023-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abq6221
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 6941: Show issues

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Article: Plasmacytoid Dendritic Cell, Slan

Pettinella, Francesca / Lattanzi, Chiara / Donini, Marta / Caveggion, Elena / Marini, Olivia / Iannoto, Giulia / Costa, Sara / Zenaro, Elena / Fortunato, Tiago Moderno / Gasperini, Sara / Giani, Matteo / Belluomini, Lorenzo / Sposito, Marco / Insolda, Jessica / Scaglione, Ilaria Mariangela / Milella, Michele / Adamo, Annalisa / Poffe, Ornella / Bronte, Vincenzo /

Dusi, Stefano / Cassatella, Marco A / Ugel, Stefano / Pilotto, Sara / Scapini, Patrizia

Cancers

2023 Volume 15, Issue 21

Abstract: The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients ... ...

Abstract	The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan
Language	English
Publishing date	2023-11-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15215285
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