Mr. Grisetti earned a Bachelor's degree in Natural Sciences from the Università degli Studi di Milano and a Master's in Functional Genomics from the Università degli Studi di Trieste, focusing on serum microRNAs as biomarkers for hepatocellular carcinoma (HCC).
He completed a Ph.D. in Molecular Biomedicine at the University of Trieste, researching Aurora kinase A (AURKA) as a driver of hepatocarcinogenesis and immune evasion. After six months as a research fellow at the Italian Liver Foundation, he joined IRCCS De Bellis in Castellana Grotte, where he continues to work on liver cancer research.
EDUCATION
09/2014 – 07/2017 Milano, Italy
Bachelor's degree in Natural Science, Università degli Studi di Milano, Milano, Italy
11/2020 – 05/2024 Trieste, Italy
PH.D. student in molecular biomedicine, Università degli Studi di Trieste, Trieste, Italy
10/2017 – 07/2020 Trieste, Italy
Master's degree in Functional Genomics, Università degli Studi di Trieste, Trieste, Italy
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Molecular Biology, Molecular Medicine, Hepatology
5
Scopus Publications
48
Scholar Citations
4
Scholar h-index
1
Scholar i10-index
Scopus Publications
Subtype-dependent PD-L1 stability and immune context shape immunotherapy response in hepatocellular carcinoma Luca Grisetti, Clarissa J. C. Garcia, Paola Tarchi, Claudio Tiribelli, Devis Pascut Frontiers in Immunology, 2026 Introduction Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have expanded treatment options for hepatocellular carcinoma (HCC), yet only a subset of patients achieves durable responses. Limited efficacy reflects gaps in understanding PD-L1 regulation, including its biochemical heterogeneity, subtype-specific stability, and effects on tumor–immune interactions. We aimed to dissect these mechanisms and identify integrated biomarkers predictive of immunotherapy response. Methods Human HCC and paired non-tumoral tissues, an HBV-driven transgenic mouse model, and five HCC cell lines representing Hoshida/Caruso subtypes were analyzed. PD-L1 expression, glycosylation, and stability were assessed by Western blot, flow cytometry, and immunohistochemistry. Functional assays included co-cultures of HCC cells with primary activated PBMCs from multiple healthy donors. Cells were treated with durvalumab or atezolizumab, in the presence or absence of IFN-γ stimulation. PD-L1 turnover was evaluated using cycloheximide and proteasome inhibition. Results PD-L1 protein was increased in ~60% of tumors, particularly in virally driven HCC. Elevated PD-L1 in non-tumoral liver was associated with higher recurrence risk. Biochemical profiling revealed multiple PD-L1 species: mature N-glycosylated and intermediate forms indicative of enhanced stability were enriched in tumors. Glycosylated PD-L1 displayed prolonged half-life in S1/CL3 subtypes, whereas S2/CL1 cells exhibited rapid, proteasome-dependent turnover. PD-L1 abundance alone did not predict immune susceptibility: S1-like cells, despite higher PD-L1, were highly sensitive to CD8 + T-cell–mediated killing and PD-L1 blockade, whereas S2-like cells were more resistant to cytotoxicity. ICIs induced donor-dependent cytotoxicity, with variable responder profiles; durvalumab outperformed atezolizumab, consistent with reduced glycosylation dependence. IFN-γ priming enhanced PD-L1 expression and restored immune responsiveness in low-responder co-cultures. Overall, tumors with stable glycosylated PD-L1 (S1-like) rely on PD-L1–mediated immune suppression and may benefit from PD-L1–targeted therapies, whereas tumors with low or rapidly turned-over PD-L1 (S2-like) exhibit dynamic PD-L1 regulation with increased reliance on de novo synthesis, limiting responsiveness to PD-L1 blockade alone and supporting the need for combinatorial approaches. Conclusions PD-L1 regulation in HCC depends on molecular subtype, post-translational stability, and host immune competence. Integrating these factors provides a framework for guiding patient selection and optimizing immunotherapy.
The ncRNA-AURKA Interaction in Hepatocellular Carcinoma: Insights into Oncogenic Pathways, Therapeutic Opportunities, and Future Challenges Clarissa Joy C. Garcia, Luca Grisetti, Claudio Tiribelli, Devis Pascut Life, 2024 Hepatocellular carcinoma (HCC) represents a major public health concern and ranks among the leading cancer-related mortalities globally. Due to the frequent late-stage diagnosis of HCC, therapeutic options remain limited. Emerging evidence highlights the critical role of non-coding RNAs (ncRNAs) in the regulation of Aurora kinase A (AURKA), one of the key hub genes involved in several key cancer pathways. Indeed, the dysregulated interaction between ncRNAs and AURKA contributes to tumor development, progression, and therapeutic resistance. This review delves into the interplay between ncRNAs and AURKA and their role in hepatocarcinogenesis. Recent findings underscore the involvement of the ncRNAs and AURKA axis in tumor development and progression. Furthermore, this review also discusses the clinical significance of targeting ncRNA-AURKA axes, offering new perspectives that could lead to innovative therapeutic strategies aimed at improving outcomes for HCC patients.
The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer Luca Grisetti, Clarissa J. C. Garcia, Anna A. Saponaro, Claudio Tiribelli, Devis Pascut Cell Proliferation, 2024 Aurora Kinase A (AURKA) plays a central role as a serine/threonine kinase in regulating cell cycle progression and mitotic functions. Over the years, extensive research has revealed the multifaceted roles of AURKA in cancer development and progression. AURKA's dysregulation is frequently observed in various human cancers, including hepatocellular carcinoma (HCC). Its overexpression in HCC has been associated with aggressive phenotypes and poor clinical outcomes. This review comprehensively explores the molecular mechanisms underlying AURKA expression in HCC and its functional implications in cell migration, invasion, epithelial‐to‐mesenchymal transition, metastasis, stemness, and drug resistance. This work focuses on the clinical significance of AURKA as a diagnostic and prognostic biomarker for HCC. High levels of AURKA expression have been correlated with shorter overall and disease‐free survival in various cohorts, highlighting its potential utility as a sensitive prognostic indicator. Recent insights into AURKA's role in modulating the tumour microenvironment, particularly immune cell recruitment, may provide valuable information for personalized treatment strategies. AURKA's critical involvement in modulating cellular pathways and its overexpression in cancer makes it an attractive target for anticancer therapies. This review discusses the evidence about novel and selective AURKA inhibitors for more effective treatments for HCC.
Biomarkers for the Detection and Management of Hepatocellular Carcinoma in Patients Treated with Direct-Acting Antivirals Loraine Kay D. Cabral, Luca Grisetti, Muhammad Yogi Pratama, Claudio Tiribelli, Devis Pascut Cancers, 2022 Hepatocellular carcinoma (HCC) is the sixth-most common type of cancer worldwide and chronic Hepatitis C virus (HCV) represents the main etiological factor in developed countries. HCV promotes hepatocarcinogenesis through persistent liver inflammation and dysregulation of cell signaling pathways. The introduction of direct-acting antivirals (DAAs) resulted in a significant improvement in the eradication of the virus, with an expected reduction of HCC incidence. However, the risk of HCC development can persist after DAA treatment. Recent studies have investigated the potential use of molecular biomarkers that predict HCC occurrence or recurrence helping the stratification of patients under surveillance. This review aimed to summarize all pre-clinical exploration of predictive biomarkers to identify DAA-treated patients at risk for HCC development. Dysregulated microRNAs, lncRNAs, histone modifications, cytokines, proteins, and sphingolipids represent various classes of HCC risk predictors identified in two different biological sources (tissue and serum). The non-invasive serum markers can provide a more accessible means to perform clinical monitoring and predict the risk of HCC. In addition, conditions like cirrhosis, predisposing to HCC, strongly correlate with most of the molecular predictors identified, supporting the value of these molecules as possible biomarkers of HCC in DAA-treated patients.
MiR-3201 as a Prognostic Blood Biomarker for Curative Treatments in Hepatocellular Carcinoma Luca Grisetti, Niệm Văn Thành Võ, Như Nhật Quỳnh Nguyễn, Lory Saveria Crocè, Alessia Visintin, et al. Technology in Cancer Research and Treatment, 2022 Background: Hepatic resection, radiofrequency ablation (RF), and liver transplantation (LT) represent the only available curative treatments for early stage hepatocellular carcinoma (HCC). Various studies showed that the 5-year overall survival (OS) rate reaches ∼70% after resection and ∼60% after RF. Objective: To improve the success rate of curative therapies and consequently the OS, an improvement in patients’ selection and management should be pursued. In this regard, microRNAs (miRNAs) can be helpful prognostic biomarkers. Materials and Methods: In this retrospective study, a miRNA array profiling was performed on 34 HCC blood samples which is collected before therapy (T0), 1 month (T1), and 6 months (T2) after curative treatments (resection and RF) to identify noninvasive biomarker candidates for therapy response and OS. MiRNAs were validated in 80 blood HCC samples using quantitative real-time PCR (qRT-PCR). Patients were divided into complete responder (CR) and partial responder and progressive disease (PRPD). Results: Among the selected miRNAs, miR-3201 is significantly associated with treatment response in the validation phase, showing a 23% reduction ( P = .026) in CR compared to PRPD. MiR-3201 was able to distinguish CR from PRPD (area under the curve [AUC] = 0.69, 71% sensitivity, 70% specificity, P = .0036). Furthermore, lower levels of miR-3201 were associated with longer OS (hazard ratio [HR] = 2.61, P = .0006). Conclusions: Blood miR-3201 could be used as a prognostic biomarker for curative therapy response and OS in HCC.
RECENT SCHOLAR PUBLICATIONS
Subtype-dependent PD-L1 stability and immune context shape immunotherapy response in hepatocellular carcinoma L Grisetti, CJC Garcia, P Tarchi, C Tiribelli, D Pascut Frontiers in Immunology 17, 1822947 , 2026 2026
The ncRNA-AURKA Interaction in Hepatocellular Carcinoma: Insights into Oncogenic Pathways, Therapeutic Opportunities, and Future Challenges CJC Garcia, L Grisetti, C Tiribelli, D Pascut Life 14 (11), 1430 , 2024 2024 Citations: 3
The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer L Grisetti, CJC Garcia, AA Saponaro, C Tiribelli, D Pascut Cell Proliferation 57 (8), e13641 , 2024 2024 Citations: 27
FRI-516-YI Aurora kinase A and programmed death-ligand 1: Expression dynamics in hepatocellular carcinoma development and the regulatory role of the kinase in immune checkpoint … L Grisetti, AA Saponaro, C Sukowati, D Bonazza, E Giacomello, P Tarchi, ... Journal of Hepatology 80, S429-S430 , 2024 2024 Citations: 1
The Role of Aurora Kinase A in the Development of Hepatocellular Carcinoma and in the Regulation of Programmed Death-Ligand 1 L Grisetti Università degli Studi di Trieste , 2024 2024
The expression of Aurora Kinase A and its potential role as a regulator of Programmed Death-Ligand 1 in hepatocellular carcinoma: Implications for immunotherapy and immune … L Grisetti, AA Saponaro, CHC Sukowati, P Tarchi, LS Crocè, S Palmisano, ... Digestive and Liver Disease 55, S219-S220 , 2023 2023 Citations: 4
MiR-3201 as a prognostic blood biomarker for curative treatments in hepatocellular carcinoma L Grisetti, NVT Võ, NNQ Nguyễn, LS Croce, A Visintin, C Tiribelli, ... Technology in cancer research & treatment 21, 15330338221132924 , 2022 2022 Citations: 7
Biomarkers for the detection and management of hepatocellular carcinoma in patients treated with direct-acting antivirals LKD Cabral, L Grisetti, MY Pratama, C Tiribelli, D Pascut Cancers 14 (11), 2700 , 2022 2022 Citations: 6
MOST CITED SCHOLAR PUBLICATIONS
The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer L Grisetti, CJC Garcia, AA Saponaro, C Tiribelli, D Pascut Cell Proliferation 57 (8), e13641 , 2024 2024 Citations: 27
MiR-3201 as a prognostic blood biomarker for curative treatments in hepatocellular carcinoma L Grisetti, NVT Võ, NNQ Nguyễn, LS Croce, A Visintin, C Tiribelli, ... Technology in cancer research & treatment 21, 15330338221132924 , 2022 2022 Citations: 7
Biomarkers for the detection and management of hepatocellular carcinoma in patients treated with direct-acting antivirals LKD Cabral, L Grisetti, MY Pratama, C Tiribelli, D Pascut Cancers 14 (11), 2700 , 2022 2022 Citations: 6
The expression of Aurora Kinase A and its potential role as a regulator of Programmed Death-Ligand 1 in hepatocellular carcinoma: Implications for immunotherapy and immune … L Grisetti, AA Saponaro, CHC Sukowati, P Tarchi, LS Crocè, S Palmisano, ... Digestive and Liver Disease 55, S219-S220 , 2023 2023 Citations: 4
The ncRNA-AURKA Interaction in Hepatocellular Carcinoma: Insights into Oncogenic Pathways, Therapeutic Opportunities, and Future Challenges CJC Garcia, L Grisetti, C Tiribelli, D Pascut Life 14 (11), 1430 , 2024 2024 Citations: 3
FRI-516-YI Aurora kinase A and programmed death-ligand 1: Expression dynamics in hepatocellular carcinoma development and the regulatory role of the kinase in immune checkpoint … L Grisetti, AA Saponaro, C Sukowati, D Bonazza, E Giacomello, P Tarchi, ... Journal of Hepatology 80, S429-S430 , 2024 2024 Citations: 1
Subtype-dependent PD-L1 stability and immune context shape immunotherapy response in hepatocellular carcinoma L Grisetti, CJC Garcia, P Tarchi, C Tiribelli, D Pascut Frontiers in Immunology 17, 1822947 , 2026 2026
The Role of Aurora Kinase A in the Development of Hepatocellular Carcinoma and in the Regulation of Programmed Death-Ligand 1 L Grisetti Università degli Studi di Trieste , 2024 2024
Publications
MiR-3201 as a Prognostic Blood Biomarker for Curative Treatments in Hepatocellular Carcinoma
Luca Grisetti, Niem Văn Thành Võ, Nhu Nhat Quynh Nguyen, Lory Saveria Crocè, Alessia Visintin, Claudio Tiribelli, Devis Pascut
DOI: 10.1177/15330338221132924
Biomarkers for the Detection and Management of Hepatocellular Carcinoma in Patients Treated with Direct-Acting Antivirals
Loraine Kay D. Cabral †, Luca Grisetti †, Muhammad Yogi Pratama, Claudio Tiribelli, Devis Pascut
† These authors contributed equally to this work.
DOI: 10.3390/cancers14112700
