Expression Of Th22 Cells And Its Functional Cytokine IL-22 And Myeloid-derived Suppressor Cells In Elderly Gastric Cancer Patients

Objective: Aging is a slow,common,and degenerative biological process.Currently,uncovering the mystery of aging and interfering with it has aroused the interest of geriatricians worldwide.Research process of aging has produced many theories,such as free radical,mitochondrial,telomere,stress theory and so on.Recently inflammatory-aging and immune senescence are thought as means of clarifying the relationship with other theories,so are getting more attention.Chronic low-grade inflammation and immunosuppression which are closely related to inflammatory-aging and immune senescence not only accompany aging but also play an important role in maintaining and promoting the aging process.Epidemiological data show that chronic inflammation and immunosuppression are associated with age-related diseases.For example cancer often occurs in the elderly which is closely related to their inflammatory and immune background.Research emphasis on inflammatory and immunity in the elderly is beneficial to delaying aging and age-related diseases(such as cancer).Th22 cells which secrete pro-inflammatory cytokine IL-22 and Myeloid-derived suppressor cells(MDSCs)have been demonstrated in autoimmune inflammatory and neoplastic disease,whether they are involved in the aging process and participate in the development of elderly gastric cancer are still unknown.This study by investigating Th22 cells and its functional cytokine IL-22 and MDSCs in different ages,cancer and non-cancer subjects will try to reveal the correlation between aging,inflammation,and immunity.The result aims to provide new ideas for Geriatrics and Immunology.Methods: Fresh peripheral blood was obtained from 39 elderly gastric cancer patients(EGC)from the First Affiliated Hospital of Dalian Medical University(aged 65-91 years),as well as from 32 elderly healthy controls(HE)(aged 65-90 years)and 31 young healthy controls(HY)(aged 24-35 years)in our study.Peripheral Th22,Th17,Th1 cells,and MDSCs were determined by flow cytometry.The level of plasma IL-22,IL-6,and TNF-? were examined by enzyme-linked immunosorbent assay.IL-22 protein levels in another 40 elderly gastric cancer tissue samples were measured by immunohistochemistry.Results:1.Peripheral Th22 cells was higher in HE as compared to HY(0.79±0.27% vs.0.36±0.21%,P < 0.001),and was even higher in EGC(1.16±0.33%,P < 0.001)compared to HE;peripheral Th17 cells in EGC were greater than in HE(2.91±0.93% vs.2.24±0.79%,P<0.001),HE were greater than HY(1.50±0.63%,P<0.001;compared to HE(1.59±0.98%)or HY(1.53±0.88%),peripheral MDSCs levels in EGC were significantly increased(3.06±1.01%,P < 0.001).There was a positive correlation between the percentage of Th22 and Th17 cells in studied subjects(r=0.699,P<0.001);Moreover positive correlations were found between the percentage of MDSCs and Th22,Th17 cells in EGC(r=0.479,P=0.002 and r=0.420,P=0.008);besides positive correlations were found between the percentage of MDSCs and Th22,Th17 cells in EGC(r=0.479,P=0.002 and r=0.420,P=0.008),the proportion of them were higher in advanced gastric cancer patients(P<0.05).2.In EGC,HE,and HY,the plasma IL-22 levels respectively were(151.45±33.56pg/ ml,123.31±22.80pg/ml and 109.25±28.50pg/ml);plasma IL-6 levels were(45.90± 8.60pg/ml,26.68±7.23pg/ml and 18.17±7.95pg/ml);plasma TNF-? levels were(59.70±17.38pg/ml,38.66±12.94pg/ml and 27.40±11.97pg/ml),among them plasma IL-22 levels were significantly increased in EGC than HE,HY(P<0.001),and plasma IL-22 levels in patients were greater in advanced stages of the disease(P<0.01).In these three groups of subjects there was a significant difference regarding plasma IL-6,TNF-? levels(P<0.05).There was a positive correlation between percentages of Th22 cells and plasma IL-22,IL-6,TNF-?(r=0.636,r=0.798 and r=0.714,P<0.001).3.Immunohistochemistry showed that IL-22 was mainly distributed in the tumor cells and infiltrating lymphocytes around the tumor.Conclusions: Our study shows that peripheral Th22,Th17 cells,plasma IL-6,and TNF-? levels increased with aging.Peripheral Th22,Th17 cells,MDSCs,and IL-22 are crucial to the progression of gastric cancer in elderly,which can provide new ideas for tumor immunotherapy.