Association between natural killer cell activity
and colorectal cancer in high-risk subjects
undergoing colonoscopy.

 

Jobin G., Rodriguez-Suarez R., Betito K., Gastroenterology (2017), doi:10.1053/j.gastro.2017.06.009.

 

This study was accepted for publication in Gastroenterology on June 11, 2017. It is currently in press. You can access a pdf of the unedited manuscript at: http://www.gastrojournal.org/article S0016-5085(17)35743-8/pdf

 

Clinical study details

 

BACKGROUND & AIMS:

Low activity of natural killer (NK) cells has been associated with increased risk of cancer and has been reported in patients with colorectal cancer (CRC). Activity of NK cells can be measured in a small volume of whole blood by a commercially available test. We investigated whether this test could be used to identify patients with CRC, using findings from colonoscopy as a reference standard.

 

METHODS:

We performed an open-label, prospective, cross-sectional study of 872 high-risk subjects (more than 40 years old) screened for CRC by colonoscopy at a university hospital in Montreal, Canada from October 2014 through January 2016. Blood samples were collected on the day of colonoscopy, prior to the procedure. The test involves stimulation of whole blood with cytokines that induce NK cells to secrete interferon gamma (IFNG), which is quantified by an ELISA. Tissue samples were taken from lesions during the colonoscopy and analyzed histologically; subjects were classified as having no evidence of disease, adenomatous polyps of less than 10 mm, of 10 mm or more, or CRC. We used the non-parametric Mann-Whitney test to compare NK cell activity between subjects with no evidence of CRC and subjects found to have CRC. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the test to identify individuals with CRC. The primary objective was to determine the difference in NK cell activity between subjects with vs without CRC. The secondary objective was the test performance, based on ROC analysis, and cut-off value that most accurately identified individuals with CRC.

 

RESULTS:

We found a significant difference in NK cell activity between the 23 subjects with CRC (based on pathology analysis) and the 849 subjects without CRC: subjects found to have CRC by colonoscopy had a median level of 86.0 pg IFNG/mL (inter-quartile range, 43.3-151.0 pg IFNG/mL), whereas subjects without CRC had a median level of 298.1 pg IFNG/mL (inter-quartile range, 100.4-920.2 pg IFNG/mL) (P=.0002). The cut-off value that most accurately identified subjects with CRC was 181 pg/mL. The NK cell activity test identified subjects with CRC with 87.0% sensitivity, 60.7% specificity, a positive predictive value of 5.7%, and a negative predictive value of 99.4%. The odds ratio for detection of CRC in subjects with low NK cell activity vs subjects with higher NK cell activity was 10.3 (95% CI, 3.03-34.9).

 

CONCLUSIONS:

Using colonoscopy as the reference standard, a test for NK cell activity in whole blood samples identified patients with CRC with 87.0% sensitivity and a negative predictive value of 99.4%. Subjects with low NK cell activity had a 10-fold higher risk of CRC compared to subjects with high NK cell activity. This test might be used in clinical practice to assess patients for risk of CRC. Clinicaltrials.gov number: NCT02291198.

 

About NK Vue

NK Vue is the first commercially available IVDD that measures NKA in a small volume of stimulated whole blood. This IVDD was approved by Health Canada in December 2014 for the following indication: “NK Vue is intended for in vitro diagnostic use, for the monitoring of the immune status of individuals. Measurement of NK cell activity could be a useful tool for assessing changes in immunosurveillance, which, in turn, could be indicative of a condition or disease where NK cell activity has been shown to be affected.”

 

Who is ATGen

ATGen is a public immunodiagnostic company focused on the development of in vitro diagnostic devices for the analysis of patients’ immune function. Immunosurveillance performed by lymphoid cells is important in immunity against foreign antigens and tumor cells.

 

References:   Jobin G., Rodriguez-Suarez R., Betito K., Gastroenterology (2017), doi:10.1053/j.gastro.2017.06.009.

 

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