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

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.

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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.
lmo-8-41f1.tif
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.
lmo-8-41f2a.tiflmo-8-41f2b.tiflmo-8-41f2c.tiflmo-8-41f2d.tif
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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