Valentina Pieri

Vita-Salute San Raffaele University

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Luca Bertero

University of Turin

Antonia Stammberger

University Hospital Carl Gustav Carus

Neibla Priego

Centro de Investigación del Cáncer

Leire Egia‐Mendikute

CIC bioGUNE

Matthias Meinhardt

University Hospital Carl Gustav Carus

Paola Cassoni

University of Turin

Fernando Garcı́a

Spanish National Cancer Research Centre

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Laura Álvaro‐Espinosa

Spanish National Cancer Research Centre

Marc Schmitz

TU Dresden

Alessia Pellerino

University of Milan

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Istituti di Ricovero e Cura a Carattere Scientifico

120

Vita-Salute San Raffaele University

Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele

IRCCS Ospedale San Raffaele

San Raffaele University of Rome

University of Milan

Spanish National Cancer Research Centre

University of Milano-Bicocca

European Institute of Oncology

Mario Negri Institute for Pharmacological Research

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Table S20 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells

Neibla Priego Ana de Pablos-Aragoneses María Perea-García Valentina Pieri Carolina Hernández-Oliver

Statistics of multiple experimental arms from in vivo immunotherapy experiments. Unpaired two-tailed Student’s t-test of different comparisons between the following experimental conditions: IgG2, silibinin and immune checkpoint blockade (ICB) (Anti-PD1 plus Anti-CTLA4) alone or in combination with silibinin in mice intracardially injected with B16/F10-BrM cells. Unpaired two-tailed Student’s t-test of different comparisons between the following experimental conditions: IgG2, cKOGFAP-Timp1 and immune checkpoint blockade (ICB) (Anti-PD1 plus Anti-CTLA4) alone or in combination in mice intracardially injected with E0771-BrM cells. The table contains information corresponding to Figure 7C and Supplementary Figure 8L.

Immunosuppression

10.1158/2159-8290.28193835

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Table S21 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells

Neibla Priego Ana de Pablos-Aragoneses María Perea-García Valentina Pieri Carolina Hernández-Oliver

TIMP1 levels from ELISA applied to CSF from patient samples. Levels of TIMP1 in the blood or in the cerebrospinal fluid (CSF) of non-cancer patients and brain metastasis patients from different primary tumors. Immune Cluster is shown for patients in Figure 7N. The table contains information corresponding to Figure 7L, 7N and Supplementary Figure 9A,C-D.

Immunosuppression

Table (database)

10.1158/2159-8290.28193832

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Table S11 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells

Neibla Priego Ana de Pablos-Aragoneses María Perea-García Valentina Pieri Carolina Hernández-Oliver

GSEA of CD8+ T cells incubated with pSTAT3+ conditioned media. Gene set enrichment analysis (GSEA) of top 25 upregulated and downregulated signatures and NES of Biological Process (GOBP) pathways related to T cell function comparing CD8+ in vitro cultures incubated with the pSTAT3- (d1) or pSTAT3+ (d2) secretome. The table contains information corresponding to Figure 2B.

Immunosuppression

Table (database)

10.1158/2159-8290.28193865

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Table S12 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells

Neibla Priego Ana de Pablos-Aragoneses María Perea-García Valentina Pieri Carolina Hernández-Oliver

RENACER immune cluster evaluation. Immune cluster and gene expression of immune markers in the RENACER cohort of human brain metastasis samples. The table contains information corresponding to Supplementary Figure 4C-D.

Immunosuppression

10.1158/2159-8290.28193862

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Liquid biopsy in brain tumors: moving on, slowly

Current Opinion in Oncology (2024)

Giulia Berzero Valentina Pieri L. Palazzo Gaetano Finocchiaro Massimo Filippi

Purpose of review Due to limited access to the tumor, there is an obvious clinical potential for liquid biopsy in patients with primary brain tumors. Here, we review current approaches, present limitations to be dealt with, and new promising data that may impact the field. Recent findings The value of circulating tumor cell-free DNA (ctDNA) in the cerebrospinal fluid (CSF) for the noninvasive diagnosis of primary brain tumors has been confirmed in several reports. The detection of ctDNA in the peripheral blood is desirable for patient follow-up but requires ultrasensitive methods to identify low mutant allelic frequencies. Digital PCR approaches and targeted gene panels have been used to identify recurrent hotspot mutations and copy number variations (CNVs) from CSF or plasma. Tumor classification from circulating methylomes in plasma has been actively pursued, although the need of advanced bioinformatics currently hampers clinical application. The use of focused ultrasounds to open the blood-brain barrier may represent a way to enrich of ctDNA the peripheral blood and enhance plasma-based liquid biopsy. Summary Monitoring CNVs and hotspot mutations by liquid biopsy is a promising tool to detect minimal residual disease and strengthen response assessment in patients with primary brain tumors. Novel methods to increase the relative and/or absolute amount of ctDNA can improve the clinical potential of plasma-based liquid biopsies.

Liquid biopsy

Brain tumor

Brain biopsy

Cell-free fetal DNA

Minimal Residual Disease

Circulating tumor cell

10.1097/cco.0000000000001079

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Along‐tract statistics of neurite orientation dispersion and density imaging diffusion metrics to enhance MR tractography quantitative analysis in healthy controls and in patients with brain tumors

Human Brain Mapping (2020)

Valentina Pieri Francesco Sanvito Marco Riva Alessandro Petrini Paola M. V. Rancoita

Abstract Along‐tract statistics analysis enables the extraction of quantitative diffusion metrics along specific white matter fiber tracts. Besides quantitative metrics derived from classical diffusion tensor imaging (DTI), such as fractional anisotropy and diffusivities, new parameters reflecting the relative contribution of different diffusion compartments in the tissue can be estimated through advanced diffusion MRI methods as neurite orientation dispersion and density imaging (NODDI), leading to a more specific microstructural characterization. In this study, we extracted both DTI‐ and NODDI‐derived quantitative microstructural diffusion metrics along the most eloquent fiber tracts in 15 healthy subjects and in 22 patients with brain tumors. We obtained a robust intraprotocol reference database of normative along‐tract microstructural metrics, and their corresponding plots, from healthy fiber tracts. Each diffusion metric of individual patient's fiber tract was then plotted and statistically compared to the normative profile of the corresponding metric from the healthy fiber tracts. NODDI‐derived metrics appeared to account for the pathological microstructural changes of the peritumoral tissue more accurately than DTI‐derived ones. This approach may be useful for future studies that may compare healthy subjects to patients diagnosed with other pathological conditions.

Fiber tract

10.1002/hbm.25291

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VERDICT MRI estimates match histopathology features in brain tumours

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition (2023)

Matteo Figini Antonella Castellano Michele Bailo Marcella Callea Valentina Pieri

We recently adapted the VERDICT framework to characterize both the core and peritumoural areas of brain tumours. We report here its first clinical application in the differentiation of brain tumour histotypes. Comparing groups of lesions with increasing aggressiveness (from lower to higher grades to metastases) we observed a significant increase in the intracellular and vascular fraction in the lesion core. VERDICT maps matched the features showed by histopathology in lower grades and in metastases; in the most heterogeneous higher grades, VERDICT maps showed differences between subregions compatible with histopathology results in multiple biopsy samples.

Histopathology

Verdict

10.58530/2022/0545

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Figure S7 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells

Neibla Priego Ana de Pablos-Aragoneses María Perea-García Valentina Pieri Carolina Hernández-Oliver

TIMP1 binding to CD63 modulates kinase signaling in CD8+ T cells. Supplementary Figure 7 shows additional data corresponding to Figure 6.

Immunosuppression

10.1158/2159-8290.28193883

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Table S6 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells

Neibla Priego Ana de Pablos-Aragoneses María Perea-García Valentina Pieri Carolina Hernández-Oliver

Human brain metastasis samples analyzed with Chromium Fixed RNA Profiling. Clinical information of human brain metastasis samples included in Figure 1F-I.

Immunosuppression

Human brain

10.1158/2159-8290.28193808

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Automated Steerable Path Planning for Deep Brain Stimulation Safeguarding Fiber Tracts and Deep Gray Matter Nuclei

Frontiers in Robotics and AI (2019)

Alice Segato Valentina Pieri Alberto Favaro Marco Riva Andrea Falini

Deep Brain Stimulation (DBS) is a neurosurgical procedure consisting in the stereotactic implantation of stimulation electrodes to specific brain targets, such as deep gray matter nuclei. Current solutions to place the electrodes rely on rectilinear stereotactic trajectories (RTs) manually defined by surgeons, based on pre-operative images. An automatic path planner that accurately targets subthalamic nuclei (STN) and safeguards critical surrounding structures is still lacking. Also, robotically-driven curvilinear trajectories (CTs) computed on the basis of state-of-the-art neuroimaging would decrease DBS invasiveness, circumventing patient-specific obstacles. This work presents a new algorithm able to estimate a pool of DBS curvilinear trajectories for reaching a given deep target in the brain, in the context of the EU's Horizon EDEN2020 project. The prospect of automatically computing trajectory plans relying on sophisticated newly engineered steerable devices represents a breakthrough in the field of microsurgical robotics. By tailoring the paths according to single-patient anatomical constraints, as defined by advanced preoperative neuroimaging including diffusion MR tractography, this planner ensures a higher level of safety than the standard rectilinear approach. 10 healthy controls underwent Magnetic Resonance Imaging (MRI) on 3T scanner, including 3DT1-weighted sequences, 3Dhigh‐resolution time‐of‐flight MR angiography (TOF-MRA) and high angular resolution diffusion MR sequences. A probabilistic q-ball residual-bootstrap MR tractography algorithm was used to reconstruct motor fibers, while the other deep gray matter nuclei surrounding STN and vessels were segmented on T1 and TOF-MRA images, respectively. These structures were labelled as obstacles. The reliability of the automated planner was evaluated; CTs were compared to RTs in terms of efficacy and safety. Targeting the anterior STN, CTs performed significantly better in maximizing the minimal distance from critical structures, by finding a tuned balance between all obstacles. Moreover, CTs resulted superior in reaching the center of mass (COM) of STN, as well as in optimizing the entry angle in STN and in the skull surface.

Fiber tract

Gray (unit)

Fast marching method

10.3389/frobt.2019.00070

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Citations (22)