Abstract

BACKGROUND:Digestive malignancies, especially pancreaticcancer (PC), gastric cancer (GC), and colorectal cancer (CRC), still occur atpersistently high rates, and disease progression in these cancers has beenassociated with tumor immunosurveillance escape. Natural killer (NK) celldysfunction may be responsible for this phenomenon, however, the exactrelationship between tumor immunosurveillance escape in digestive malignanciesand NK cell dysfunction remains unclear.

METHODS:Percentage of the surface receptors NKG2A, KIR3DL1,NKG2D, NKp30, NKp44, NKp46, and DNAM-1, as well as the cytotoxic granulesperforin and granzyme B positive NK cells were determined in patients withpancreatic cancer (n=31), gastric cancer (n=31), and CRC (n=32) prior tosurgery and healthy controls (n=31) by multicolor flow cytometry. Independentt-tests or Mann-Whitney U-tests were used to compare the differences betweenthe patient and healthy control groups, as well as the differences betweenpatients with different pathologic features of cancer.

RESULTS:Percentage of NKG2D, NKp30, NKp46, and perforinpositive NK cells was significantly down-regulated in patients with PC comparedto healthy controls, as well as GC and CRC; reduced levels of these moleculeswas associated with indicators of disease progression in each malignancy (suchas histological grade, depth of invasion, lymph node metastasis). On thecontrary, percentage of KIR3DL1 positive NK cells was significantly increasedin patients with PC, as well as GC and CRC, but was not associated with anyindicators of disease progression.

CONCLUSIONS:Altered percentage of surface receptors andcytotoxic granules positive NK cells may play a vital role in tumorimmunosurveillance escape by inducing NK cell dysfunction in patients with PC,GC, and CRC.