Publications by authors named "Mario Paolo Colombo"

Breast cancer is the most frequent type of tumor in women and is characterized by variable outcomes due to its heterogeneity and the presence of many cancer cell-autonomous and -non-autonomous factors. A major determinant of breast cancer aggressiveness is represented by immune infiltration, which can support tumor development. In our work, we studied the role of mast cells in breast cancer and identified a novel activity in promoting the tumor-initiating properties of cancer cells.

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  • The study investigates the distinct regions of the germinal center (GC)—the dark zone (DZ) and light zone (LZ)—which are crucial for B-cell expansion and antibody maturation, yet lack a clear understanding of their immune composition differences.
  • Researchers discovered specific DNA damage responses and chromatin features that explain why T-cells are excluded from the DZ region, providing insights into its immune-repulsive characteristics.
  • The findings highlight the role of the ATR kinase in regulating responses in the DZ, suggesting that targeting ATR could enhance immunotherapy effectiveness for aggressive types of lymphoma like Diffuse Large B-cell Lymphomas (DLBCL).
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  • NAMPT is an important enzyme involved in NAD homeostasis and is linked to increased levels of a released form (eNAMPT) in inflammatory conditions and breast cancer, with levels correlating to patient prognosis.* -
  • In experiments with mice, the use of a neutralizing antibody (C269) against eNAMPT resulted in smaller tumors and fewer metastases, showing the potential of targeting eNAMPT in cancer treatment.* -
  • The study reveals that neutralizing eNAMPT enhances T-cell responses by affecting the PD-L1/PD-1 pathway, which could help to overcome the immunosuppressive environment in triple negative breast cancer.*
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  • - Oncological treatments are evolving quickly with the introduction of targeted therapies, leading to a focus on combining these new methods with traditional care, particularly in radioimmunotherapy.
  • - The review explores the synergistic effects of radiotherapy and immunotherapy, discussing who might benefit, the significance of abscopal effects, and what factors clinicians consider in treatment.
  • - There is a need for more research to support the evidence for combined therapies, as addressing these unanswered questions is crucial for integrating radioimmunotherapy into standard clinical practices.
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  • Researchers studied a type of lung cancer called Non Small Cell Lung Cancer (NSCLC) and found that the commonly used test for a protein called PD-L1 is not very good at showing how well treatments will work, especially in patients with low levels of this protein.
  • They looked at tiny particles from the blood, called EVs, in 64 patients with low PD-L1 who were treated with immune therapies, and found that those who responded better to treatment had specific markers on their EVs.
  • The study suggests that measuring certain markers on these EVs could help doctors figure out which patients are more likely to benefit from immune therapies for their cancer.
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Introduction: Lipid metabolism impacts immune cell differentiation, activation, and functions, modulating inflammatory mediators, energy homeostasis, and cell membrane composition. Despite preclinical evidence, data in humans lack concerning tumors and immunotherapy (IO). We aimed at investigating the correlations between circulating lipids and the outcome of non-small cell lung cancer (NSCLC) patients treated with IO.

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Purpose: The stromal and immune bone marrow (BM) landscape is emerging as a crucial determinant for acute myeloid leukemia (AML). Regulatory T cells (Treg) are enriched in the AML microenvironment, but the underlying mechanisms are poorly elucidated. Here, we addressed the effect of IFNγ released by AML cells in BM Treg induction and its impact on AML prognosis.

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Tumor outcome is determined not only by cancer cell-intrinsic features but also by the interaction between cancer cells and their microenvironment. There is great interest in tumor-infiltrating immune cells, yet mast cells have been less studied. Recent work has highlighted the impact of mast cells on the features and aggressiveness of cancer cells, but the eventual effect of mast cell infiltration is still controversial.

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Nonsense-mediated mRNA decay (NMD) is a highly conserved cellular surveillance mechanism, commonly studied for its role in mRNA quality control because of its capacity of degrading mutated mRNAs that would produce truncated proteins. However, recent studies have proven that NMD hides more complex tasks involved in a plethora of cellular activities. Indeed, it can control the stability of mutated as well as non-mutated transcripts, tuning transcriptome regulation.

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In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments.

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Purpose: Little is known about the efficacy of HER2-targeted therapy in patients with breast cancer showing different HER2-pathway dependence and immune phenotypes. Herein, we report a NeoALTTO exploratory analysis evaluating the clinical value of 22 types of tumor-infiltrating immune cells by CIBERSORT and 5 immune-related metagenes in the overall patient population, and in subgroups defined by the TRAR classifier as HER2-addicted (TRAR-low) or not (TRAR-high).

Patients And Methods: Association of baseline TRAR, immune-related metagenes, and CIBERSORT data with pathologic complete response (pCR) and event-free survival (EFS) were assessed using logistic and Cox regression models.

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  • A study was conducted to explore how the innate immune system interacts with a combination of TLR9 agonists and anti-PD-1 antibodies in combating tumors, using immunodeficient mice to eliminate T cell influence.
  • The research found that the anti-PD-1 antibody reduced the effectiveness of TLR9 therapy by altering macrophage behavior, leading these immune cells to adopt a phenotype that suppresses antitumor activity.
  • Depleting macrophages in vivo countered this negative effect, suggesting that active TLR signaling in macrophages can be disrupted by anti-PD-1 treatment, potentially aiding tumor progression.
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In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy.

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Lung is a specialized tissue where metastases from primary lung tumors takeoff and those originating from extra-pulmonary sites land. One commonality characterizing these processes is the supportive role exerted by myeloid cells, particularly neutrophils, whose recruitment is facilitated in this tissue microenvironment. Indeed, neutrophils have important part in the pathophysiology of this organ and the key mechanisms regulating neutrophil expansion and recruitment during infection can be co-opted by tumor cells to promote growth and metastasis.

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  • Researchers transplanted human neural precursor cells from stem cells into the brains of mice and rats, observing that the cells successfully survived and differentiated for about a month before being rejected.
  • The transplants lasted longer in NOD-SCID mice, which have a compromised immune system, suggesting that immune tolerance played a role in cell survival.
  • Mixing the human cells with partially differentiated cells or a cellular extract from adult rat cerebellum improved the longevity of the transplants, indicating that adjusting the developmental stage of the cells may enhance immune tolerance during transplantation.
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Background: Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells impact on the diversification of aggressive lymphoma clones is still unknown.

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  • This content can include videos, images, interactive elements, or downloadable resources.
  • It's designed to enhance understanding and engagement with the main material.
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Background: The rapid spread of coronavirus disease (COVID-19) is affecting many countries. While healthcare systems need to cope with the need to treat a large number of people with different degrees of respiratory failure, actions to preserve aliquots of the healthcare system to guarantee treatment to patients are mandatory.

Methods: In order to protect the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano from the spread of COVID-19, a number of to-hospital and within-hospital filters were applied.

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  • Inflammation significantly contributes to cardiac disease, driven primarily by macrophages and T lymphocytes, but other immune cell subsets’ roles remain unclear.
  • The study utilized single-cell RNA sequencing to analyze immune cell composition in a mouse model of heart failure, identifying various immune subsets at different disease stages and comparing results with human samples.
  • Findings revealed that beyond traditional immune players, a broader range of cells, including neutrophils, B cells, and mast cells, becomes activated during heart failure, prompting further research into these immune interactions in cardiac health.
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Background: Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy.

Methods: Patients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.

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Objectives: Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO.

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