Decreased NKG2D expression on CD8+ T cell is involved in immune evasion in patients with gastric cancer.
OBJECTIVE
Some studies suggest that the immunoreceptor NKG2D expression on CD8(+) T cells is down-regulated and this reduction may be involved in immune evasion in cancer patients. The present study was designed to investigate NKG2D expression on CD8(+) T lymphocytes and its relationship to immune evasion in gastric cancer patients.


METHODS
NKG2D expression on both circulating and tumor-infiltrating CD8(+) T cells was evaluated by multicolor flow cytometry. Soluble MHC class I chain-related gene A (MICA) in the sera was quantitated by ELISA. Transwell experiments were carried out to determine the effect of cancer cells on NKG2D expression.


RESULTS
NKG2D expression on circulating CD8(+) T cells was down-regulated and significantly correlated with IFN-gamma production in gastric cancer patients (r = 0.68; P = 0.007). NKG2D expression was closely related to undifferentiated cancer (P = 0.021) as was the depth of invasion (P = 0.012). There was no difference in soluble MICA between gastric cancer patients and normal controls. NKG2D expression on CD8(+) T cells was remarkably reduced in the tissue of gastric cancer compared with peripheral blood (P = 0.046). Complete removal of tumor by surgery restored NKG2D expression on CD8(+) T cells (P = 0.0049). Transwell experiments showed that this down-regulation was induced by direct contact between cancer cells and CD8(+) T cells and that soluble factors did not affect the NKG2D expression. This phenomenon was blocked by the addition of anti-MICA antibodies.


CONCLUSIONS
Decreased NKG2D expression may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer.
Osaki
Tomohiro
T
Department of Surgery, Division of Surgical Oncology, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago 683-8504, Japan.
Saito
Hiroaki
H
Yoshikawa
Toshiaki
T
Matsumoto
Sachiko
S
Tatebe
Shigeru
S
Tsujitani
Shunichi
S
Ikeguchi
Masahide
M
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D055607:Receptors, Natural Killer Cell; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma