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CLINICOPATHOLOGIC CHARACTERISTICS ASSOCIATED WITH NATURAL KILLER CELL ACTIVITY BY MEASUREMENT OF INTERFERON-GAMMA IN HEMATOLOGIC MALIGNANCIES
Author(s): ,
Sholhui Park
Affiliations:
Laboratory Medicine,Ewha Womans University College of Medicine,Seoul,Korea, Republic Of
,
Yeung Chul Mun
Affiliations:
Internal Medicine,Ewha Womans University College of Medicine,Seoul,Korea, Republic Of
,
Chu-Myong Seong
Affiliations:
Internal Medicine,Ewha Womans University College of Medicine,Seoul,Korea, Republic Of
,
Hee Jin Huh
Affiliations:
Laboratory Medicine,Dongguk University, Ilsan Medical Center,Ilsan,Korea, Republic Of
Jungwon Huh
Affiliations:
Laboratory Medicine,Ewha Womans University College of Medicine,Seoul,Korea, Republic Of
(Abstract release date: 05/19/16) EHA Library. Huh J. 06/09/16; 134510; PB1610
Prof. Jungwon Huh
Prof. Jungwon Huh
Contributions
Abstract
Abstract: PB1610

Type: Publication Only

Background
Natural killer (NK) cells play a key role in innate immune responses and an important component of anti-cancer defenses. Evaluation of NK cell activity could be invaluable to estimate the status and the outcome of cancers. Defects in NK cell cytotoxicity have been reported in hematologic malignancies. Conventional methods such as 51Cr release assay and CD107a degranulation assay may be useful to determine NK cell activity, but they require complex experimental setups and are not appropriate for routine laboratory test. Recently, a commercialized kit for measurement of NK cell activity was developed, which measure released interferon-gamma secreted by ex vivo stimulated NK cells in whole blood. 

Aims
The purpose of this study was to investigate clinicopathologic characteristics associated with NK cell activity by measurement of interferon-gamma. 

Methods
The study group included 134 patients (61 at diagnosis and 73 at follow up) diagnosed as having hematologic malignancies between Mar 2015 and Jan 2016. The NK cell activity was measured by commercialized kit (NK Vue assay, ATgen, Sungnam, Korea), which is a quantitative sandwich ELISA to measure released interferon-gamma secreted by NK cells in whole blood collected in PROMOCA tube (an engineered recombinant cytokine that specifically activates NK cells). NK cell activity was expressed as ratio which patient’s result was divided by upper normal level. NK cell activity was analyzed using 294 specimens obtained from patients at diagnosis or follow up. 

Results
The median ratio value of NK cell activity was 1.27 (range: 0.03-8.0). Comparing with NK cell activity of 61 patients at diagnosis (12 AML, 5 ALL, 3 CML, 2 MDS/MPN, 11 MM, 25 lymphoma, 3 solid cancer), ALL patients had significantly decreased NK cell activity (median: 0.16, range: 0.16-0.26) than lymphoma patients (median: 1.05, range: 0.03-2.35, P=0.0196). No significant differences were found among other hematologic malignancies at diagnosis.Among the total patients including at diagnosis and follow up, NK cell activity was positively correlated with percentage of lymphocytes (r=0.346, P<0.0001), whereas NK cell activity showed weak negative associations with total WBC counts (r=-0.126, P=0.0324), neutrophil counts (r=-0.155, P=0.0083) and NLR (neutrophil/lymphocyte ratio) (r=-0.227, P<0.0001). Of particular, NK cell activity had positive correlations with percentage of lymphocytes in patients with AML (r=0.693, P=0.0125), lymphoma (r=0.502, P<0.0001) and multiple myeloma (r=0.427, P=0.0011). The regression analysis between NK cell activity and lymphocyte subsets identified by flow cytometry (CD56+ NK cell, CD3+ T-cell, CD4+ T-cell and CD19+ B-cell) did not show significant associations except for CD8+ T cell counts (r=0.159, P=0.0083). The CRP didn’t show a significant association with NK cell activity(r=0.126, P=0.6076). 

Conclusion
This study showed that the NK cell activity was significantly decreased in ALL patients, comparing with that of lymphoma patients and NK cell activity was not correlated with NK cell counts identified by flow cytometry. NK cell assay by measurement of interferon-gamma secreted by ex vivo stimulated NK cells in whole blood, could be useful to evaluate and monitor the NK cell activity in hematologic malignancies.   

Session topic: E-poster

Keyword(s): CD56, Hematological malignancy, Interferon gamma, Natural killer
Abstract: PB1610

Type: Publication Only

Background
Natural killer (NK) cells play a key role in innate immune responses and an important component of anti-cancer defenses. Evaluation of NK cell activity could be invaluable to estimate the status and the outcome of cancers. Defects in NK cell cytotoxicity have been reported in hematologic malignancies. Conventional methods such as 51Cr release assay and CD107a degranulation assay may be useful to determine NK cell activity, but they require complex experimental setups and are not appropriate for routine laboratory test. Recently, a commercialized kit for measurement of NK cell activity was developed, which measure released interferon-gamma secreted by ex vivo stimulated NK cells in whole blood. 

Aims
The purpose of this study was to investigate clinicopathologic characteristics associated with NK cell activity by measurement of interferon-gamma. 

Methods
The study group included 134 patients (61 at diagnosis and 73 at follow up) diagnosed as having hematologic malignancies between Mar 2015 and Jan 2016. The NK cell activity was measured by commercialized kit (NK Vue assay, ATgen, Sungnam, Korea), which is a quantitative sandwich ELISA to measure released interferon-gamma secreted by NK cells in whole blood collected in PROMOCA tube (an engineered recombinant cytokine that specifically activates NK cells). NK cell activity was expressed as ratio which patient’s result was divided by upper normal level. NK cell activity was analyzed using 294 specimens obtained from patients at diagnosis or follow up. 

Results
The median ratio value of NK cell activity was 1.27 (range: 0.03-8.0). Comparing with NK cell activity of 61 patients at diagnosis (12 AML, 5 ALL, 3 CML, 2 MDS/MPN, 11 MM, 25 lymphoma, 3 solid cancer), ALL patients had significantly decreased NK cell activity (median: 0.16, range: 0.16-0.26) than lymphoma patients (median: 1.05, range: 0.03-2.35, P=0.0196). No significant differences were found among other hematologic malignancies at diagnosis.Among the total patients including at diagnosis and follow up, NK cell activity was positively correlated with percentage of lymphocytes (r=0.346, P<0.0001), whereas NK cell activity showed weak negative associations with total WBC counts (r=-0.126, P=0.0324), neutrophil counts (r=-0.155, P=0.0083) and NLR (neutrophil/lymphocyte ratio) (r=-0.227, P<0.0001). Of particular, NK cell activity had positive correlations with percentage of lymphocytes in patients with AML (r=0.693, P=0.0125), lymphoma (r=0.502, P<0.0001) and multiple myeloma (r=0.427, P=0.0011). The regression analysis between NK cell activity and lymphocyte subsets identified by flow cytometry (CD56+ NK cell, CD3+ T-cell, CD4+ T-cell and CD19+ B-cell) did not show significant associations except for CD8+ T cell counts (r=0.159, P=0.0083). The CRP didn’t show a significant association with NK cell activity(r=0.126, P=0.6076). 

Conclusion
This study showed that the NK cell activity was significantly decreased in ALL patients, comparing with that of lymphoma patients and NK cell activity was not correlated with NK cell counts identified by flow cytometry. NK cell assay by measurement of interferon-gamma secreted by ex vivo stimulated NK cells in whole blood, could be useful to evaluate and monitor the NK cell activity in hematologic malignancies.   

Session topic: E-poster

Keyword(s): CD56, Hematological malignancy, Interferon gamma, Natural killer

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