Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma
| العنوان: | Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma |
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| المؤلفون: | Salvatore Albani, Chun Jye Lim, Richard Hoau Gong Lo, Lu Pan, Sharifah Nur Hazirah, Camillus Chua, Valerie Chew, Rene L F Filarca, Liyun Lai, Alexander Y. F. Chung, Pierce K. H. Chow, Nurul J M Nasir, Tony Kiat-Hon Lim, Yun Hua Lee, Brian K. P. Goh, David Chee Eng Ng |
| المصدر: | Gut |
| بيانات النشر: | BMJ, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Carcinoma, Hepatocellular, Antigen-Presenting Cells, Peripheral blood mononuclear cell, immune activation, Granzymes, CCL5, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Immune system, Y90 radioembolization, Biomarkers, Tumor, tumor microenvironment, Humans, Medicine, Yttrium Radioisotopes, chemotaxis, Chemokine CCL5, CXCL16, Singapore, Tumor microenvironment, Hepatology, Tumor Necrosis Factor-alpha, business.industry, Liver Neoplasms, Gastroenterology, biomarkers, hepatocellular carcinoma, Chemokine CXCL16, Flow Cytometry, Natural killer T cell, Granzyme B, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Disease Progression, Leukocytes, Mononuclear, Cancer research, Female, Time-of-flight Mass Cytometry (CyTOF), business, CD8 |
| الوصف: | ObjectivesYttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response.DesignTime-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE.ResultsTILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8+ T cells, CD56+ NK cells and CD8+ CD56+ NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GB+CD8+ T cells to the Y90-RE-treated tumours. When comparing PBMCs before and after Y90-RE, we observed an increase in tumour necrosis factor-α on both the CD8+ and CD4+ T cells as well as an increase in percentage of antigen-presenting cells after Y90-RE, implying a systemic immune activation. Interestingly, a high percentage of PD-1+/Tim-3+CD8+ T cells coexpressing the homing receptors CCR5 and CXCR6 denoted Y90-RE responders. A prediction model was also built to identify sustained responders to Y90-RE based on the immune profiles from pretreatment PBMCs.ConclusionHigh-dimensional analysis of tumour and systemic immune landscapes identified local and systemic immune activation that corresponded to the sustained response to Y90-RE. Potential biomarkers associated with a positive clinical response were identified and a prediction model was built to identify sustained responders prior to treatment. |
| تدمد: | 1468-3288 0017-5749 |
| DOI: | 10.1136/gutjnl-2017-315485 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57d63fd8d19ceb8a200adb9e055133e6 https://doi.org/10.1136/gutjnl-2017-315485 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....57d63fd8d19ceb8a200adb9e055133e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14683288 00175749 |
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| DOI: | 10.1136/gutjnl-2017-315485 |