Tommaso Maria Marvulli

RESEARCH, TEACHING, or OTHER INTERESTS

Biomedical Engineering, Molecular Biology, Artificial Intelligence, Bioengineering

Scopus Publications

Developing a risk score using liquid biopsy biomarkers for selecting Immunotherapy responders and stratifying disease progression risk in metastatic melanoma patients
Amalia Azzariti, Simona De Summa, Tommaso M. Marvulli, Ivana De Risi, Giuseppe De Palma, Roberta Di Fonte, Rossella Fasano, Simona Serratì, Sabino Strippoli, Letizia Porcelli,et al.
Springer Science and Business Media LLC
Abstract Background Despite the high response rate to PD-1 blockade therapy in metastatic melanoma (MM) patients, a significant proportion of patients do not respond. Identifying biomarkers to predict patient response is crucial, ideally through non-invasive methods such as liquid biopsy. Methods Soluble forms of PD1, PD-L1, LAG-3, CTLA-4, CD4, CD73, and CD74 were quantified using ELISA assay in plasma of a cohort of 110 MM patients, at baseline, to investigate possible correlations with clinical outcomes. A clinical risk prediction model was applied and validated in pilot studies. Results No biomarker showed statistically significant differences between responders and non-responders. However, high number of significant correlations were observed among certain biomarkers in non-responders. Through univariate and multivariate Cox analyses, we identified sPD-L1, sCTLA-4, sCD73, and sCD74 as independent biomarkers predicting progression-free survival and overall survival. According to ROC analysis we discovered that, except for sCD73, values of sPD-L1, sCTLA-4, and sCD74 lower than the cut-off predicted lower disease progression and reduced mortality. A comprehensive risk score for predicting progression-free survival was developed by incorporating the values ​​of the two identified independent factors, sCTLA-4 and sCD74, which significantly improved the accuracy of outcome prediction. Pilot validations highlighted the potential use of the risk score in treatment-naive individuals and long responders. Conclusion In summary, risk score based on circulating sCTLA-4 and sCD74 reflects the response to immune checkpoint inhibitor (ICI) therapy in MM patients. If confirmed, through further validation, these findings could assist in recommending therapy to patients likely to experience a long-lasting response.


Immunosuppressive therapy and oral anticoagulation in kidney transplant recipients: Direct oral anticoagulants versus vitamin-k antagonists
Francesco Santoro, Annalisa Casanova, Simona Simone, Carlo Alfieri, Adele Falcone, Andrea Dello Strologo, Valeria Grandinetti, Marco Busutti, Giorgia Comai, Tommaso Maria Marvulli,et al.
Elsevier BV



Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma
Simona Serratì, Roberta Di Fonte, Letizia Porcelli, Simona De Summa, Ivana De Risi, Livia Fucci, Eustachio Ruggieri, Tommaso Maria Marvulli, Sabino Strippoli, Rossella Fasano,et al.
Springer Science and Business Media LLC
Abstract Background Clinical drawback in checkpoint inhibitors immunotherapy (ICI) of metastatic melanoma (MM) is monitoring clinical benefit. Soluble forms of PD1(sPD1) and PD-L1(sPD-L1) and extracellular vesicles (EVs) expressing PD1 and PD-L1 have recently emerged as predictive biomarkers of response. As factors released in the blood, EVs and soluble forms could be relevant in monitoring treatment efficacy and adaptive resistance to ICI. Methods We used pre-therapy plasma samples of 110 MM patients and longitudinal samples of 46 patients. Elisa assay and flow cytometry (FCM) were used to measure sPD-L1 and sPD1 concentrations and the percentage of PD1+ EVs and PD-L1+ EVs, released from tumor and immune cells in patients subsets. Transwell assays were conducted to investigate the impact of EVs of each patient subset on MM cells invasion and interaction between tumor cells and macrophages or dendritic cells. Viability assays were performed to assess EVs effect on MM cells and organoids sensitivity to anti-PD1. FCM was used to investigate immunosuppressive markers in EVs and immune cells. Results The concentrations of sPD1 and sPD-L1 in pre-treatment and longitudinal samples did not correlate with anti-PD1 response, instead only tumor-derived PD1+ EVs decreased in long responders while increased during disease progression in responders. Notably, we observed reduction of T cell derived EVs expressing LAG3+ and PD1+ in long responders and their increase in responders experiencing progression. By investigating the impact of EVs on disease progression, we found that those isolated from non-responders and from patients with progression disease accelerated tumor cells invasiveness and migration towards macrophages, while EVs of long responders reduced the metastatic potential of MM cells and neo-angiogenesis. Additionally, the EVs of non-responders and of progression disease patients subset reduced the sensitivity of MM cells and organoids of responder to anti-PD1 and the recruitment of dendritic cells, while the EVs of progression disease subset skewed macrophages to express higher level of PDL-1. Conclusion Collectively, we suggest that the detection of tumor-derived PD1 + EVs may represent a useful tool for monitoring the response to anti-PD1 and a role for EVs shed by tumor and immune cells in promoting tumor progression and immune dysfunction. Graphical Abstract


A Serious Game for the Assessment of Visuomotor Adaptation Capabilities during Locomotion Tasks Employing an Embodied Avatar in Virtual Reality
Vladimiro Suglia, Antonio Brunetti, Guido Pasquini, Mariapia Caputo, Tommaso Maria Marvulli, Elena Sibilano, Sara Della Bella, Paola Carrozza, Chiara Beni, David Naso,et al.
MDPI AG
The study of visuomotor adaptation (VMA) capabilities has been encompassed in various experimental protocols aimed at investigating human motor control strategies and/or cognitive functions. VMA-oriented frameworks can have clinical applications, primarily in the investigation and assessment of neuromotor impairments caused by conditions such as Parkinson’s disease or post-stroke, which affect the lives of tens of thousands of people worldwide. Therefore, they can enhance the understanding of the specific mechanisms of such neuromotor disorders, thus being a potential biomarker for recovery, with the aim of being integrated with conventional rehabilitative programs. Virtual Reality (VR) can be entailed in a framework targeting VMA since it allows the development of visual perturbations in a more customizable and realistic way. Moreover, as has been demonstrated in previous works, a serious game (SG) can further increase engagement thanks to the use of full-body embodied avatars. Most studies implementing VMA frameworks have focused on upper limb tasks and have utilized a cursor as visual feedback for the user. Hence, there is a paucity in the literature about VMA-oriented frameworks targeting locomotion tasks. In this article, the authors present the design, development, and testing of an SG-based framework that addresses VMA in a locomotion activity by controlling a full-body moving avatar in a custom VR environment. This workflow includes a set of metrics to quantitatively assess the participants’ performance. Thirteen healthy children were recruited to evaluate the framework. Several quantitative comparisons and analyses were run to validate the different types of introduced visuomotor perturbations and to evaluate the ability of the proposed metrics to describe the difficulty caused by such perturbations. During the experimental sessions, it emerged that the system is safe, easy to use, and practical in a clinical setting. Despite the limited sample size, which represents the main limitation of the study and can be compensated for with future recruitment, the authors claim the potential of this framework as a useful instrument for quantitatively assessing either motor or cognitive impairments. The proposed feature-based approach gives several objective parameters as additional biomarkers that can integrate the conventional clinical scores. Future studies might investigate the relation between the proposed biomarkers and the clinical scores for specific disorders such as Parkinson’s disease and cerebral palsy.


The role of unpaired image-to-image translation for stain color normalization in colorectal cancer histology classification
Nicola Altini, Tommaso Maria Marvulli, Francesco Alfredo Zito, Mariapia Caputo, Stefania Tommasi, Amalia Azzariti, Antonio Brunetti, Berardino Prencipe, Eliseo Mattioli, Simona De Summa,et al.
Elsevier BV



Multi-class Tissue Classification in Colorectal Cancer with Handcrafted and Deep Features
Nicola Altini, Tommaso Maria Marvulli, Mariapia Caputo, Eliseo Mattioli, Berardino Prencipe, Giacomo Donato Cascarano, Antonio Brunetti, Stefania Tommasi, Vitoantonio Bevilacqua, Simona De Summa,et al.
Springer International Publishing



Combining autoencoder and artificial neural network for classifying colorectal cancer stages