File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1136/gutjnl-2022-IDDF.30
- Find via
Supplementary
-
Citations:
- Appears in Collections:
Conference Paper: HLA-E/NKG2A hampers tumor surveillance of natural killer cells induced by TLR4-mediated hepatic senescence
Title | HLA-E/NKG2A hampers tumor surveillance of natural killer cells induced by TLR4-mediated hepatic senescence |
---|---|
Authors | |
Issue Date | 4-Sep-2022 |
Publisher | BMJ Publishing Group |
Abstract | Background Hepatocellular carcinoma (HCC) recurrence occurs at a rate of 10–20% within 5 years after Liver transplantation (LT). Graft injury during LT significantly affects tumor recurrence by immunological regulation. However, the role of natural killer (NK) cells in HCC recurrence was not understood. Methods 346 HCC patients who underwent LT were recruited. The correlation between NKG2A+NK cells and tumor recurrence was analyzed. The cytotoxic function of NKG2A+NK cells was evaluated by co-culture with HCC cells by LDH assay. Hepatic ischemia-reperfusion injury plus major hepatectomy (IRI+Hx) in C57bl/6 mice was established. Tumor cells (Hepa 1–6) were injected into the liver via the portal vein. Results GWR (the ratio of graft volume to estimated liver volume) < 60% was an independent risk factor for early tumour recurrence after LT (IDDF2022-ABS-0267 Figure 1). The frequencies of circulating and intra-graft NK cells were lower in GWR < 60% patients post-LT (IDDF2022-ABS-0267 Figure 2). NK cells in GWR < 60% patients expressed lower Granzyme B and IFN-γ, whereas higher inhibitory marker NKG2A (IDDF2022-ABS-0267 Figure 3A, IDDF2022-ABS-0267 Figure 3B), along with increased expressions of its ligand HLA-E and inflammatory signatures. HLA-E was significantly correlated with TLR4 (IDDF2022-ABS-0267 Figure 3C). The cytotoxic function of NKG2A+NK cells was significantly decreased as they expressed lower activating markers and decreased cytokines (IDDF2022-ABS-0267 Figure 4A). When co-cultured with HCC cells, NKG2A+NK cells were with less cytotoxicity (IDDF2022-ABS-0267 Figure 4B). In IRI+Hx mouse model, liver-resident NK cells shifted to liver infiltrated NK cells after IRI+Hx, with increased expressions of NKG2A on NK cells and hepatic HLA-E mRNA (IDDF2022-ABS-0267 Figure 5A). After tumor cell injection, NKG2A+ liver-resident NK cells were increased in IRI+Hx group compared to the controls (IDDF2022-ABS-0267 Figure 5B). Senescent hepatocytes were significantly induced after hepatic IRI+Hx (IDDF2022-ABS-0267 Figure 6A). Furtherly, upregulation of NKG2A on NK cells was induced by co-cultured with senescent hepatocytes (IDDF2022-ABS-0267 Figure 6B). |
Persistent Identifier | http://hdl.handle.net/10722/333758 |
ISSN | 2023 Impact Factor: 23.0 2023 SCImago Journal Rankings: 8.052 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yang, Xinxiang | - |
dc.contributor.author | Man, Kwan | - |
dc.contributor.author | Ng, Kevin Tak Pan | - |
dc.date.accessioned | 2023-10-06T08:38:50Z | - |
dc.date.available | 2023-10-06T08:38:50Z | - |
dc.date.issued | 2022-09-04 | - |
dc.identifier.issn | 0017-5749 | - |
dc.identifier.uri | http://hdl.handle.net/10722/333758 | - |
dc.description.abstract | <p><strong>Background</strong> Hepatocellular carcinoma (HCC) recurrence occurs at a rate of 10–20% within 5 years after Liver transplantation (LT). Graft injury during LT significantly affects tumor recurrence by immunological regulation. However, the role of natural killer (NK) cells in HCC recurrence was not understood.</p><p><strong>Methods</strong> 346 HCC patients who underwent LT were recruited. The correlation between NKG2A+NK cells and tumor recurrence was analyzed. The cytotoxic function of NKG2A+NK cells was evaluated by co-culture with HCC cells by LDH assay. Hepatic ischemia-reperfusion injury plus major hepatectomy (IRI+Hx) in C57bl/6 mice was established. Tumor cells (Hepa 1–6) were injected into the liver via the portal vein.</p><p><strong>Results</strong> GWR (the ratio of graft volume to estimated liver volume) < 60% was an independent risk factor for early tumour recurrence after LT (IDDF2022-ABS-0267 Figure 1). The frequencies of circulating and intra-graft NK cells were lower in GWR < 60% patients post-LT (IDDF2022-ABS-0267 Figure 2). NK cells in GWR < 60% patients expressed lower Granzyme B and IFN-γ, whereas higher inhibitory marker NKG2A (IDDF2022-ABS-0267 Figure 3A, IDDF2022-ABS-0267 Figure 3B), along with increased expressions of its ligand HLA-E and inflammatory signatures. HLA-E was significantly correlated with TLR4 (IDDF2022-ABS-0267 Figure 3C). The cytotoxic function of NKG2A+NK cells was significantly decreased as they expressed lower activating markers and decreased cytokines (IDDF2022-ABS-0267 Figure 4A). When co-cultured with HCC cells, NKG2A+NK cells were with less cytotoxicity (IDDF2022-ABS-0267 Figure 4B). In IRI+Hx mouse model, liver-resident NK cells shifted to liver infiltrated NK cells after IRI+Hx, with increased expressions of NKG2A on NK cells and hepatic HLA-E mRNA (IDDF2022-ABS-0267 Figure 5A). After tumor cell injection, NKG2A+ liver-resident NK cells were increased in IRI+Hx group compared to the controls (IDDF2022-ABS-0267 Figure 5B). Senescent hepatocytes were significantly induced after hepatic IRI+Hx (IDDF2022-ABS-0267 Figure 6A). Furtherly, upregulation of NKG2A on NK cells was induced by co-cultured with senescent hepatocytes (IDDF2022-ABS-0267 Figure 6B).</p> | - |
dc.language | eng | - |
dc.publisher | BMJ Publishing Group | - |
dc.relation.ispartof | International Digestive Disease Forum (04/09/2022-04/09/2022, Hong Kong) | - |
dc.title | HLA-E/NKG2A hampers tumor surveillance of natural killer cells induced by TLR4-mediated hepatic senescence | - |
dc.type | Conference_Paper | - |
dc.identifier.doi | 10.1136/gutjnl-2022-IDDF.30 | - |
dc.identifier.volume | 71 | - |
dc.identifier.issue | Suppl 2 | - |
dc.identifier.eissn | 1468-3288 | - |
dc.identifier.issnl | 0017-5749 | - |