Publications by authors named "Simone Puccio"
Background: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive biliary tract cancer with a poor prognosis and a complex tumour microenvironment (TME) that remains poorly understood.
Objective: This study aimed to investigate the phenotypic and molecular characteristics of B lymphocytes, their interactions with the TME and their prognostic implications.
Design: B-cell compartments in the tumour, peritumour, and peripheral blood of iCCA patients were analysed using multimodal single-cell technologies.
Tumor evolution is one of the major mechanisms responsible for acquiring therapy-resistant and more aggressive cancer clones. Whether the tumor microenvironment through immune-mediated mechanisms might promote the development of more aggressive cancer types is crucial for the identification of additional therapeutic opportunities. Here, we identify a subset of tumor-associated neutrophils, defined as tumor-associated neutrophil precursors (PreNeu).
View Article and Find Full Text PDFInfiltration of macrophages into tumors is a hallmark of cancer progression, and re-educating tumor-associated macrophages (TAMs) toward an antitumor status is a promising immunotherapy strategy. However, the mechanisms through which cancer cells affect macrophage education are unclear, limiting the therapeutic potential of this approach. Here we conducted an unbiased genome-wide CRISPR screen of primary macrophages.
View Article and Find Full Text PDFGlioblastoma is invariably lethal and responds poorly to immune checkpoint blockade. Here, we examined the impact of regulatory T (Treg) cell depletion on glioblastoma progression and immunotherapy responsiveness. In human glioblastoma, elevated Treg cell signatures correlated with poorer survival outcomes, with these cells expressing high levels of CD25.
View Article and Find Full Text PDFMetastasis is the spread of cancer cells from primary tumours to distant organs and is the cause of 90% of cancer deaths globally. Metastasizing cancer cells are uniquely vulnerable to immune attack, as they are initially deprived of the immunosuppressive microenvironment found within established tumours. There is interest in therapeutically exploiting this immune vulnerability to prevent recurrence in patients with early cancer at risk of metastasis.
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- High-dimensional cytometry (HDC) is a cutting-edge technology for analyzing single-cell characteristics in complex biological systems, but existing analytical methods are often too complex for most lab scientists.
- Development of an analytical framework, cyCONDOR, aims to simplify the analysis process by offering comprehensive tools that cover essential steps from data preprocessing to biological interpretation.
- cyCONDOR enhances the analysis of HDC data with features like guided pre-processing, clustering, and advanced analytical tools, enabling researchers to gain deeper insights efficiently and apply findings in clinical settings.
Background: Heart failure (HF) is strongly associated with inflammation. In pressure overload (PO)-induced HF, cardiac stress triggers adaptive immunity, ablation or inhibition of which blocks disease progression. We hypothesized that PO-HF might fulfill the often-used criteria of autoimmunity: if so, the associated adaptive immune response would be not only necessary but also sufficient to induce HF; it should also be possible to identify self-antigens driving the autoimmune response.
View Article and Find Full Text PDFNaCl enhances CD8 T cell effector functions in cancer immunotherapy.
Nat Immunol
October 2024
Article Synopsis
- CD8 T cells are crucial for controlling tumors but often become dysfunctional in the tumor environment; sodium chloride (NaCl) has been found to counteract this dysfunction and promote cancer regression.
- Supplementing NaCl during CD8 T cell culture enhances their activation and effectiveness while preserving key gene networks associated with T cell plasticity, leading to improved anti-tumor responses in mouse models.
- The research suggests that NaCl affects CD8 T cell function by boosting their glutamine consumption, which is essential for their overall effectiveness, indicating potential new strategies for enhancing cancer immunotherapy in humans.
Article Synopsis
- - Esophageal cancer is a deadly type of cancer, accounting for 5% of cancer-related deaths, with two main types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the latter of which is less studied.
- - The study used advanced single-cell RNA sequencing to identify immune cell types and genes that influence anti-tumor responses in EAC, assessing their potential to predict patient outcomes post-surgery.
- - The findings suggest new immunological biomarkers for EAC that can help personalize treatment strategies, improve prognosis predictions, and aid in patient follow-up after surgery.
Article Synopsis
- Iron homeostasis is crucial for organisms as it facilitates essential biochemical functions but can be toxic in excess, which is regulated by the protein Fur in bacteria.
- The HpFur protein in Helicobacter pylori uniquely acts as a transcriptional commutator, with its apo- and holo- forms serving as different repressors that bind DNA in distinct ways for various target genes.
- The study proposes a comprehensive redefinition of holo-HpFur regulatory targets using RNA-seq and ChIP-seq data, uncovering new coding sequences and non-coding RNAs influenced by iron availability, thereby enriching the understanding of this protein's regulatory roles.
Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach.
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- Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a treatment for blood cancers that relies on effective immune reconstitution (IR) to prevent severe infections like Human Cytomegalovirus (HCMV).
- The study reveals that specific types of Natural Killer (NK) cells, called KIR NK cells, significantly contribute to controlling HCMV due to their early recovery and strong antiviral properties.
- Maintaining high levels of KIR NK cells post-transplant can serve as a predictor for HCMV infection risk and could lead to improved treatments by boosting these immune cells in donor lymphocyte infusions.
Flow cytometry (FCM) can investigate dozens of parameters from millions of cells and hundreds of specimens in a short time and at a reasonable cost, but the amount of data that is generated is considerable. Computational approaches are useful to identify novel subpopulations and molecular biomarkers, but generally require deep expertize in bioinformatics and the use of different platforms. To overcome these limitations, we introduce CRUSTY, an interactive, user-friendly webtool incorporating the most popular algorithms for FCM data analysis, and capable of visualizing graphical and tabular results and automatically generating publication-quality figures within minutes.
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- Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment for blood cancers, but patients often face recurrent infections post-transplant.
- A study conducted on 19 patients receiving CD45RA-depleted donor lymphocyte infusions (DLI) found that this approach enhances the immune response without increasing risks associated with naïve T-cells.
- Results showed that specific memory T-cells, particularly those targeting cytomegalovirus (CMV), proliferated significantly and maintained their presence for at least a month post-infusion, suggesting better protection against viral infections.
High-Dimensional Single-Cell Profiling of Tumor-Infiltrating CD4 Regulatory T Cells.
Methods Mol Biol
October 2022
Article Synopsis
- - CD4 T regulatory cells (Tregs) are a specialized type of T lymphocyte that help maintain immune balance and suppress tumor growth by limiting the activity of effector T cells.
- - Recent advancements in high-dimensional single-cell technologies, including single-cell RNA sequencing and flow cytometry, have enhanced our understanding of Treg diversity and their roles in various diseases.
- - The text presents a specific example of a high-dimensional flow cytometry analysis that identifies a Treg subpopulation associated with cancer progression, along with a general workflow for applying this analysis to any type of leukocyte.
Article Synopsis
- Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive cancer, and understanding its immune landscape, particularly the role of Tregs, is crucial for developing effective immunotherapies.
- Researchers used advanced single-cell technologies to analyze T-cell and myeloid cells in iCCA tissues and identified that while tumor-specific CD8+ T cells were poorly present, there were many hyperactivated CD4+ Tregs.
- The study found that the transcription factor MEOX1 is significantly linked to tumor-infiltrating Tregs, suggesting that targeting these activated Tregs could improve antitumor immunity in iCCA patients.
Article Synopsis
- The study investigates whether the CagY antigen plays a role in the proliferation of malignant B cells in low-grade gastric MALT lymphoma.
- Researchers compared T cell clones from patients with MALT lymphoma to those with chronic gastritis, focusing on their response to CagY and their ability to help B cell proliferation.
- Findings reveal that CagY significantly stimulates B cell proliferation and activates T cells in MALT lymphomas, suggesting its importance in this type of cancer.
Article Synopsis
- Haploidentical hematopoietic stem cell transplantation (h-HSCT) is an effective treatment for hematologic cancers, but opportunistic viral infections can negatively impact patient outcomes.
- Recent research shows that human cytomegalovirus (HCMV) plays a role in speeding up the recovery of natural killer (NK) cells post-transplant, with specific NK cell subsets showing increased presence during HCMV infection.
- The study highlights that these NK cells, while expanding, also exhibit signs of dysfunction due to changes in gene expression and exhaustion markers, affecting their ability to produce key immune signals like IFN-γ, largely influenced by viral interactions.
Article Synopsis
- Immune checkpoint inhibitors are used to treat metastatic melanoma, but only some patients respond to the treatment, highlighting the need for biomarkers to predict who might benefit.
- A study analyzed the changes in circulating CD8 T cells in 28 patients undergoing anti-PD-1 therapy, finding that responders had significantly higher levels of activated CD8 T cells and mucosal-associated invariant T (MAIT) cells compared to non-responders.
- The findings suggest that the presence of MAIT cells, particularly when they make up more than 1.7% of the peripheral CD8 population, could serve as a biomarker to identify patients likely to respond well to anti-PD-1 therapy.
Article Synopsis
- T cell memory depends on specific progenitor cells that have characteristics similar to stem cells, but their identity has been unclear until now.
- Using single-cell RNA sequencing, researchers identified two new subsets of stem-like CD8 memory T cells that differ in their epigenetic, functional, and transcriptional profiles.
- The study found that progenitors without inhibitory receptors PD-1 and TIGIT are committed to a functional lineage, while those expressing these receptors are linked to a dysfunctional, exhausted-like lineage, highlighting the complexity of T cell differentiation and its implications for immunotherapy and vaccinations.
Article Synopsis
- The interaction between Helicobacter pylori (HP) and the host is crucial for understanding the long-term persistence of the bacterium and its role in diseases like gastric cancer and autoimmune gastritis.
- Circulating antibodies can provide a "disease signature," which is valuable for early diagnostics, as symptoms often appear late in the disease's progression.
- A new approach using "phage display" and deep sequencing was employed to identify specific HP antigens recognized during immune response, leading to the discovery of unique patterns of these antigens related to different HP-related diseases.
Article Synopsis
- High-Throughput Sequencing technologies are revolutionizing research, especially in analyzing phage display libraries, by replacing tedious methods with automated sequencing.
- The InteractomeSeq web server provides a specialized tool for analyzing raw sequencing data, allowing users to define parameters for characterizing protein domains or epitopes effectively.
- This tool is significant for advancing large-scale biomarker profiling, vaccine development, and gene annotation, offering valuable resources for both scientific and clinical communities.
Article Synopsis
- Researchers have discovered that a specific transcription factor, IRF4, is expressed by a subset of CD4+ Tregs in tumors, contributing to their strong immunosuppressive abilities.
- IRF4+ Tregs exhibited higher levels of suppressive molecules and were associated with T cell exhaustion in non-small-cell lung cancer cases.
- Deleting the Irf4 gene in Tregs led to slowed tumor growth in mice, suggesting that targeting this pathway could improve cancer treatment strategies across various tumor types.