Variable Natural Killer Cell Activity in Hematological Malignancies at Diagnosis

Sholhui Park; Yeung Chul Mun; Chu-Myong Seong; Hee Jin Huh; Jungwon Huh

doi:10.3343/lmo.2018.8.2.41

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Park, Mun, Seong, Huh, and Huh: Variable Natural Killer Cell Activity in Hematological Malignancies at Diagnosis

Original Article

Lab Med Online 2018;8(2):41-51.

Published online: 19 April 2018

DOI: https://doi.org/10.3343/lmo.2018.8.2.41

Variable Natural Killer Cell Activity in Hematological Malignancies at Diagnosis

Sholhui Park, M.D.¹, Yeung Chul Mun, M.D.², Chu-Myong Seong, M.D.², Hee Jin Huh, M.D.^∗,³, Jungwon Huh, M.D.^∗,¹

¹Departments of Laboratory Medicine, Ewha Womans University, College of Medicine, Seoul, Korea

²Departments of Internal Medicine, Ewha Womans University, College of Medicine, Seoul, Korea

³Department of Laboratory Medicine, Dongguk University Ilsan Hospital, Goyang, Korea

Corresponding author: Jungwon Huh Department of Laboratory Medicine, Ewha Womans University, College of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea Tel: +82-2-2650-5320, Fax: +82-2-2650-5091, E-mail: JungWonH@ewha.ac.kr

Co-corresponding author: Hee Jin Huh Department of Laboratory Medicine, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang 10326, Korea Tel: +82-31-961-7893, Fax: +82-31-961-7902, E-mail: hjhuh@duih.org

Received 20 July 2017 Revised 29 November 2017 Accepted 29 November 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Natural killer (NK) cells play a key role in innate immune responses and are an important component of anti-cancer defenses. This study aimed to investigate the clinicopathological characteristics of NK cell activity (NKA) among various hematological malignancies at diagnosis and to evaluate their clinical value as a monitoring marker.

Methods:

A total of 111 patients that were newly diagnosed with hematological malignancies were recruited, comprising 18 acute myeloid leukemia (AML), 31 multiple myeloma (MM), and 62 lymphoma. Twenty-three normal control subjects from our health examination center were recruited. NKA was measured using a commercially available enzyme-linked immunosorbent assay kit, which measures interferon-gamma secreted by ex vivo-stimulated NK cells in whole blood.

Results:

The 111 patients had a median NKA of 202.80 pg/mL (range 40–2,000). NKA was significantly decreased in patients with AML (median 47.05 pg/mL, 40–2,000, P<0.0001), MM (275.00, 40–2,000, P<0.0001), and lymphoma (289.49, 40–2,000, P<0.0001) compared with that in normal controls (1,891, 412–2,000). There was a difference in NKA between AML and lymphoma (P=0.0499). Serial changes in NKA correlated with disease progression. NKA did not correlate with the NK cell count in any group of hematological malignancies.

Conclusions:

The measurement of NKA could be useful to evaluate the immunological status in hematological malignancies at diagnosis and during follow-up.

Keywords: Natural killer cells, Interferon-gamma, Clinical application, Hematological malignancy

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Fig. 1.

Comparisons of the natural killer (NK) cell activity (NKA) among patients with hematological malignancies at diagnosis and controls. Boxes are inter-quartile ranges, horizontal bars are medians, and dotted lines are 10th and 90th percentiles.

Fig. 2.

Serial analysis of natural killer (NK) cell activity (NKA) during follow-up in patients with hematological malignancies. NKA is presented as pg/mL. Abbreviations: Allo-PBSCT, allogeneic peripheral blood stem cell transplantation; Auto-PBSCT, autologous peripheral blood stem cell transplantation; CR, complete response; Dx, diagnosis; PD, progressive disease; PR, partial response; RD, relapsed disease; SD, stable disease.

Table 1.

Demographic and laboratory features of patients with hematological malignancies at diagnosis

	AML (N=18)	MM (N=31)	Lymphoma (N=62)	Normal Control (N=23)	P
Age (year)	56.5 (34–92)	70.0 (40–89)	59.5 (17–90)	51.0 (37–59)	<0.0001
Sex ratio (Male:Female)	1.57:1	1.38:1	0.82:1	0.53:1	0.2317
WBC (/µL)	3,225 (770–133,710)	5,740 (1,470–13,550)	6,585 (1,840–21,000)	4,950 (2,590–8,940)	0.0930
Neutrophil count (/µL)	480 (0–11,524)	3,796 (610–8,640)	3,874 (930–10,650)	2,690 (1,060–3,800)	0.0001
Lymphocyte count (/µL)	1,137 (540–19,114)	1,539 (310–6,998)	1,698 (190–19,320)	2,052 (1,128–4,657)	0.0756
Neutrophil / Lymphocyte (ratio)	0.31 (0.00–6.00)	2.17 (0.10–17.79)	2.49 (0.06–92.95)	1.24 (0.67–2.93)	_<0.0001
Lymphocyte percentage (%)	41.2 (8.0–83.1)	30.5 (7.1–87.8)	25.9 (2.2–92.0)	37.6 (24.0–52.1)	0.0007
NK cell activity (pg/mL)∗	47.05 (40–2,000)	275.00 (40–2,000)	289.49 (40–2,000)	1,891.00 (412–2,000)	0.1595
NK cell (CD3-/CD56+/16+) percentage (%)	11.7 (2.5–35.6)	18.9 (5.3–66.2)	15.2 (2.3–48.2)	NT	0.1276
NK cell (CD3-/CD56+/16+) count (/µL)	206 (31–4,102)	317 (48–1,489)	222 (9–1,503)	NT	0.2127
CD3+ cell count (/µL)	1,195 (461–10,464)	1,144 (215–6,353)	1,114 (142–3,818)	NT	0.5369
CD3+/CD4+ cell count (/µL)	820 (261–5,857)	550 (95–5,891)	571 (55–2,148)	NT	0.2753
CD3+/CD8+ cell count (/µL)	441 (106–4,136)	384 (7–1,436)	325 (54–1,574)	NT	0.4294
CD19+ cell count (/µL)	169 (2–4,266)	129 (11–436)	161 (6–13,955)	NT	0.6061
CRP (mg/dL)	2.00 (0.08–25.61)	0.81 (0.04–9.64)	0.51 (0.04–15.19)	NT	0.0985

Except for sex ratios, all values are medians (range). ∗Values outside of the analytical measurement range were regarded as extreme values: 40 pg/mL and 2,000 pg/mL Abbreviation: NT, not tested.

Table 2.

Correlations of NK cell activity with WBC parameters including NK cell numbers and lymphocyte subsets in patients with hematological malignancies at diagnosis

	AML (N=18)		MM (N=31)		Lymphoma (N=62)		Normal control (N=23)
	r	P	r	P	r	P	r	P
WBC count	−0.310	NS	−0.231	NS	−0.103	NS	0.325	NS
N/L ratio	−0.005	NS	−0.307	NS	−0.150	NS	0.091	NS
ANC	−0.229	NS	−0.482	0.0060	−0.283	0.0300	0.288	NS
Lymphocyte count	−0.234	NS	0.197	NS	0.148	NS	0.302	NS
Lymphocyte percentage	0.209	NS	0.373	0.0386	0.259	0.0421	0.040	NS
CRP	−0.264	NS	−0.310	NS	−0.337	0.0218	NT	NT
NK cell (CD3-/CD56+/16+ cell) count	−0.266	NS	−0.059	NS	0.172	NS	NT	NT
NK cell (CD3-/CD56+/16+ cell) percentage	−0.284	NS	−0.201	NS	−0.025	NS	NT	NT
CD3+ cell count	−0.288	NS	0.249	NS	0.188	NS	NT	NT
CD3+/CD4+ cell count	−0.285	NS	0.288	NS	0.224	NS	NT	NT
CD3+/CD8+ cell count	−0.266	NS	−0.005	NS	0.086	NS	NT	NT
CD19+ cell count	−0.298	NS	−0.100	NS	0.108	NS	NT	NT

Abbreviations: WBC, white blood cell; ANC, absolute neutrophil count; NS, not significant; N/L ratio, neutrophil to lymphocyte ratio; NT, not tested; CRP, C-reactive protein.

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