Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients
Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers p...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.899170/full |
| _version_ | 1818545962116710400 |
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| author | Maria Raffaella Petrara Sarah Shalaby Elena Ruffoni Martina Taborelli Francesco Carmona Silvia Giunco Silvia Giunco Paola Del Bianco Pierluca Piselli Diego Serraino Umberto Cillo Riccardo Dolcetti Riccardo Dolcetti Patrizia Burra Anita De Rossi Anita De Rossi |
| author_facet | Maria Raffaella Petrara Sarah Shalaby Elena Ruffoni Martina Taborelli Francesco Carmona Silvia Giunco Silvia Giunco Paola Del Bianco Pierluca Piselli Diego Serraino Umberto Cillo Riccardo Dolcetti Riccardo Dolcetti Patrizia Burra Anita De Rossi Anita De Rossi |
| author_sort | Maria Raffaella Petrara |
| collection | DOAJ |
| description | Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset. |
| first_indexed | 2024-12-12T07:46:49Z |
| format | Article |
| id | doaj.art-5930278904264ce9a73afd67bbfabe8b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T07:46:49Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5930278904264ce9a73afd67bbfabe8b2022-12-22T00:32:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.899170899170Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted PatientsMaria Raffaella Petrara0Sarah Shalaby1Elena Ruffoni2Martina Taborelli3Francesco Carmona4Silvia Giunco5Silvia Giunco6Paola Del Bianco7Pierluca Piselli8Diego Serraino9Umberto Cillo10Riccardo Dolcetti11Riccardo Dolcetti12Patrizia Burra13Anita De Rossi14Anita De Rossi15Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, ItalyMultivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, ItalyImmunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, ItalyCancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, ItalyImmunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, ItalyOncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, ItalyImmunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, ItalyClinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, ItalyClinical Epidemiology Unit, Istituto Nazionale per le Malattie Infettive (INMI) “L. Spallanzani” IRCCS, Rome, ItalyCancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, ItalyHepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, ItalySir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, AustraliaMultivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, ItalyOncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, ItalyImmunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, ItalyLiver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.https://www.frontiersin.org/articles/10.3389/fonc.2022.899170/fullimmune activationimmune senescencepost-transplant malignancyhepatocellular carcinomabiological predictors |
| spellingShingle | Maria Raffaella Petrara Sarah Shalaby Elena Ruffoni Martina Taborelli Francesco Carmona Silvia Giunco Silvia Giunco Paola Del Bianco Pierluca Piselli Diego Serraino Umberto Cillo Riccardo Dolcetti Riccardo Dolcetti Patrizia Burra Anita De Rossi Anita De Rossi Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients Frontiers in Oncology immune activation immune senescence post-transplant malignancy hepatocellular carcinoma biological predictors |
| title | Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients |
| title_full | Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients |
| title_fullStr | Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients |
| title_full_unstemmed | Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients |
| title_short | Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients |
| title_sort | immune activation exhaustion and senescence profiles as possible predictors of cancer in liver transplanted patients |
| topic | immune activation immune senescence post-transplant malignancy hepatocellular carcinoma biological predictors |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.899170/full |
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