Association between natural killer cell activity and the risk of
Yoon Suk Jung,* Min-Jung Kwon,
Dong Il Park,* Chong Il Sohn* and Jung Ho Park*
*Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, and
Department of Laboratory Medicine, Kangbuk Samsung
Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
colorectal neoplasia, natural killer cell activity.
Accepted for publication 8 October 2017.
Dr Jung Ho Park, Division of Gastroenterology,
Department of Internal Medicine Kangbuk
Samsung Hospital, Sungkyunkwan University
School of Medicine, 29, Saemunan-Ro, Jongno-
Gu, Seoul 03181, Korea.
Background and Aim: Low activity of natural killer (NK) cells is known to be associated
with higher risk of cancer, especially with poor prognosis and the presence of colorectal
cancer (CRC). We investigated whether NK cells activity differs between subjects with
and without colorectal neoplasia (CRN).
Methods: A cross-sectional study was performed on 1818 asymptomatic examinees aged
≥ 30 years who underwent NK cell activity test (which quantitates the amount of
interferon-γ secreted into the plasma by NK cells) and a colonoscopy as part of a health
Results: The mean age of the study population was 41.4 years. The proportion of overall
CRN and advanced CRN was 13.5% (n = 246) and 0.7% (n = 13), respectively. Only
one subject was diagnosed with CRC. The median level of NK cell activity was lower in
subjects with CRN than in those without CRN (1205 vs 1515 pg/mL, P = 0.009). It was
also lower in subjects with non-advanced CRN than in those without CRN (1221 vs
1515 pg/mL; P = 0.036). Moreover, it was lower in subjects with advanced CRN than in
those with non-advanced CRN (480 vs 1221 pg/mL; P = 0.028). Subjects with low levels
of NK cell activity (< 250 pg/mL) had a higher prevalence of overall CRN (19.0% vs
12.9%, P = 0.024) and advanced CRN (3.4% vs 0.4%, P = 0.001) than those who demon-
strated higher level (≥ 250 pg/mL).
Conclusions: Natural killer cell activity seemed to decrease along with CRC progression
toward the later stages in the adenoma-carcinoma sequence. Its activity may be depressed
in relation to progression of neoplasia, even at precancerous stage.
Natural killer (NK) cells are large granular lymphocytes, which
play a role in innate immunity, and are involved in the early de-
fense against infections and tumors.
NK cells of the innate im-
mune system along with the adaptive immune system orchestrate
the eradication of malignant cells.
More speciﬁcally, NK cells
link innate and cellular immunities through targeted cell death
and release of chemokines and cytokines (innate immune system),
as well as by helping adaptive immune cells in their targeted cell
elimination (adaptive immune system).
Interferon (IFN)-γ is a
major cytokine secreted from activated NK cells and exerts im-
mune responses against cancer cells.
The association between NK cell activity and cancer has been
investigated for many decades, and a reduced NK cell activity
has been known to be related with higher risk of cancer.
Japanese study including 3625 adults demonstrated that medium
and high cytotoxic activity of peripheral blood lymphocytes was
associated with reduced cancer risk (all sites), whereas low activity
was associated with increased cancer risk, suggesting a role for
natural immunological host defense mechanisms against cancer.
Additionally, several studies have focused on the relationship
between NK cell activity and colorectal cancer (CRC).
studies have shown a decreased NK cell activity in patients with
CRC when compared with healthy controls.
Other studies have
reported that reduced NK cell activity was associated with ad-
vanced stages and poor postoperative prognosis (recurrence, me-
tastasis, or low survival) among patients with CRC.
Although several studies have identiﬁed the association between
reduced NK cell activity and CRC, it remains unclear whether
NK cell activity is related to precancerous lesions, as well as
CRC. Given that most cases of CRC are sporadic and develop
through the adenoma–carcinoma sequence,
low NK cells activ-
ity may be also correlated with precancerous lesions, including co-
lorectal adenomas. However, to the best of our knowledge, there
has been no research on this topic, so far.
Established methods that measure NK cell activity, such as
release assay and CD107a degranulation assay, have been widely
used to determine NK cell function; however, these methods are
complicated and time consuming because they require isolation
of peripheral blood mononuclear cells or NK cells.
these assays sometimes require hazardous materials such as radio-
To overcome these difﬁculties, a simple assay
that uses whole blood instead of peripheral blood mononuclear
cells or isolated NK cells was developed for commercial use to
Journal of Gastroenterology and Hepatology 33 (2018) 831–836
© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd