Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients.
BACKGROUND
As a cellular membrane triggering receptor, CD226 is involved in the NK cell- or CTL-mediated lysis of tumor cells of different origin, including freshly isolated tumor cells and tumor cell lines. Here, we evaluated soluble CD226 (sCD226) levels in sera, and membrane CD226 (mCD226) expression on peripheral blood mononuclear cells (PBMC) from cancer patients as well as normal subjects, and demonstrated the possible function and origin of the altered sCD226, which may provide useful information for understanding the mechanisms of tumor escape and for immunodiagnosis and immunotherapy.


RESULTS
Soluble CD226 levels in serum samples from cancer patients were significantly higher than those in healthy individuals (P < 0.001), while cancer patients exhibited lower PBMC mCD226 expression than healthy individuals (P < 0.001). CD226-Fc fusion protein could significantly inhibit the cytotoxicity of NK cells against K562 cells in a dose-dependent manner. Furthermore, three kinds of protease inhibitors could notably increase mCD226 expression on PMA-stimulated PBMCs and Jurkat cells with a decrease in the sCD226 level in the cell culture supernatant.


CONCLUSIONS
These findings suggest that sCD226 might be shed from cell membranes by certain proteases, and, further, sCD226 may be used as a predictor for monitoring cancer, and more important, a possible immunotherapy target, which may be useful in clinical application.
Xu
Zhuwei
Z
Department of Immunology, the Fourth Military Medical University, Xi'an, PR China. xu_zhuwei@163.com
Zhang
Tao
T
Zhuang
Ran
R
Zhang
Yun
Y
Jia
Wei
W
Song
Chaojun
C
Yang
Kun
K
Yang
Angang
A
Jin
Boquan
B
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007159:Immunologic Tests / Q000639:trends; D007167:Immunotherapy / Q000639:trends; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019139:Tumor Escape; D000098862:T Lineage-Specific Activation Antigen 1
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D007141:Immunoglobulin Fc Fragments; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins