Difference in cytotoxicity against hepatocellular carcinoma between liver and periphery natural killer cells in humans

Ishiyama, K.; Ohdan, Hideki; Ohira, Masaichi; Mitsuta, Hiroshi; Arihiro, Koji; Asahara, Toshimasa

doi:10.1002/hep.21035

Cited by 168 publications

(193 citation statements)

References 49 publications

(69 reference statements)

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“…21 The underlying reason may be that TRAIL expression is highly inducible by interleukin-2 (IL-2) in liver NK cells, whereas this effect has been barely observed in peripheral NK cells. 22 This finding has recently been used in a preclinical approach to enhance the efficacy of liver transplantation, for which recurrent hepatocellular carcinoma (HCC) is one of the most fatal complications. A solution for this problem could be the adoptive transfer of IL-2-stimulated NK cells extracted from donor liver graft perfusates, as suggested by Ishiyama et al 22 IL-2-stimulated donor liver cells inductively express TRAIL and induce apoptosis in HCC without causing toxicity against 1-haplotype identical recipient intact tissues.…”

Section: Therapeutic Intervention In Liver Disease With Trail As a Pomentioning

confidence: 99%

“…22 This finding has recently been used in a preclinical approach to enhance the efficacy of liver transplantation, for which recurrent hepatocellular carcinoma (HCC) is one of the most fatal complications. A solution for this problem could be the adoptive transfer of IL-2-stimulated NK cells extracted from donor liver graft perfusates, as suggested by Ishiyama et al 22 IL-2-stimulated donor liver cells inductively express TRAIL and induce apoptosis in HCC without causing toxicity against 1-haplotype identical recipient intact tissues. These findings raise a novel concept of preventing the recurrence of HCC after liver transplantation by the adoptive transfer of IL-2-stimulated and TRAIL-expressing NK cells extracted from donor liver grafts.…”

Section: Therapeutic Intervention In Liver Disease With Trail As a Pomentioning

confidence: 99%

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On the TRAIL to therapeutic intervention in liver disease

2007

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Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The fact that HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed. HCCs are phenotypically and genetically heterogeneous tumors that commonly emerge on a background of chronic liver diseases, most of which culminate in cirrhosis, such as alcoholic cirrhosis and chronic hepatitis B and C infections. This review outlines recent findings on the progression of liver disease, including our knowledge of the role of apoptotic processes, with an emphasis on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The proapoptotic and antiapoptotic properties of TRAIL, its involvement in liver injury, and its potential as a therapeutic agent in fibrosis and HCC are discussed. Several contradictory and confusing data have not yet been resolved or placed into perspective, such as the influence of factors that determine the TRAIL sensitivity of target cells, including the tumor microenvironment or cirrhotic tissue. Therefore, we assess these data from the perspectives of gastroenterologists (P.S. and M.W.B.) and a molecular oncologist (I.H.) with research interests in liver injury, apoptosis, and experimental therapeutics. (HEPATOLOGY

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Section: Therapeutic Intervention In Liver Disease With Trail As a Pomentioning

confidence: 99%

Section: Therapeutic Intervention In Liver Disease With Trail As a Pomentioning

confidence: 99%

On the TRAIL to therapeutic intervention in liver disease

2007

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“…Furthermore, the proportion of TRAIL‐positive NK cells in LMNC significantly increased in the neoadjuvant chemotherapy group. Studies have shown TRAIL to be critical among tumor necrosis factor (TNF) family members in the NK cell‐mediated antitumor function 20, 43. Moreover, CRC cells are susceptible to TRAIL‐induced apoptosis, both as a single agent of recombinant TRAIL and combined with chemotherapy and targeted therapies 44.…”

Section: Discussionmentioning

confidence: 99%

“…We collected blood samples at the time of hepatectomy, and PBMC were isolated by gradient centrifugation with Separate‐L (Muto Pure Chemicals Co., Ltd, Tokyo, Japan) from 40 mL heparinized peripheral blood. In addition, LMNC were obtained by ex vivo perfusion through the portal vein of resected livers from CRLM patients as previously described 20. Effluents were condensed by centrifugation, and LMNC were isolated by gradient centrifugation with Separate‐L.…”

Section: Methodsmentioning

confidence: 99%

“…NK cells are part of the innate immune system and may provide a first line of defense against neoplastic cells by exerting an effector function without the necessity for priming 19. In addition, NK cells are abundant in human liver, and liver NK cells have remarkably higher cytotoxic activity against neoplastic cells than peripheral blood NK cells 20, 21. Such unique anatomical distribution and functional property of NK cells in the liver prompt us to investigate the influence of chemotherapy, particularly neoadjuvant chemotherapy, on the immunity of NK cells in the liver of CRLM patients.…”

Section: Introductionmentioning

confidence: 99%

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Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Hirata

Ishiyama

Tanaka

et al. 2018

Annals of Gastroent Surgery

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AimWe investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells.MethodsWe classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences.ResultsThere were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural‐killer group 2, member D (NKG2D)‐ positive NK cells in PBMC and percentage of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐, NKp30‐, and signal regulatory protein β (SIRPβ)‐positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)‐2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups.ConclusionColorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.

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Impact of a new liver immune status index among patients with hepatocellular carcinoma after initial hepatectomy

Imaoka

Ohira

Chogahara

et al. 2023

Annals of Gastroent Surgery

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AimThe anti‐tumor effects of natural killer (NK) cells vary among individuals. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) expressed on liver NK cells is a marker of anti‐tumor cytotoxicity against hepatocellular carcinoma (HCC) in immune cell therapy. This study aimed to develop a liver immune status index (LISI) that predicts low TRAIL expression and validates its ability to predict recurrence after initial hepatectomy for primary HCC.MethodsA functional analysis of liver NK cells co‐cultured with interleukin‐2 for 3 days was performed of 40 liver transplant donors. The LISI, which predicted low TRAIL expression (25% quartile: <33%) in liver NK cells, was calculated using multiple logistic regression analysis. Next, 586 initial hepatectomy cases were analyzed based on the LISI.ResultsOur model was based on the Fibrosis‐4 index+0.1 (odds ratio [OR], 1.33), body mass index (OR, 0.61), and albumin levels+0.1 (OR, 0.54). The area under the receiver operating characteristic curve (AUC) of the LISI for low TRAIL expression was 0.89. Stratification of the recurrence rates (RR) revealed that LISI was an independent predictive factor of RR (moderate risk: hazard ratio, 1.44; high risk: hazard ratio, 3.02). The AUC was similar for the LISI, albumin–indocyanine green evaluation grade, albumin–bilirubin score, and geriatric nutritional risk index for predicting RR. Among the vascular invasion cases, the LISI was more useful than the other indexes.ConclusionOur model facilitates the prediction of RR in high‐risk patients by providing LISI to predict the anti‐tumor effects of NK cells.

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Difference in cytotoxicity against hepatocellular carcinoma between liver and periphery natural killer cells in humans

Cited by 168 publications

References 49 publications

On the TRAIL to therapeutic intervention in liver disease

On the TRAIL to therapeutic intervention in liver disease

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Impact of a new liver immune status index among patients with hepatocellular carcinoma after initial hepatectomy

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