Immunoregulatory function of HLA-G in gastric cancer.
BACKGROUND
Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined.


METHODS
We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients.


RESULTS
There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival.


CONCLUSIONS
We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.
Department of Medical Oncology, Gata Haydarpasa Training Hospital, Istanbul, Turkey E-mail : dr_tolgatuncel@hotmail.com.
Tolga
T
Tuncel
Bulent
B
Karagoz
Aptullah
A
Haholu
Alpaslan
A
Ozgun
Levent
L
Emirzeoglu
Oguz
O
Bilgi
Emin Gokhan
EG
Kandemir
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D059951:HLA-G Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D014408:Biomarkers, Tumor; D059951:HLA-G Antigens