Infiltration and significance of tissue-resident CD8 + T cells in gastric cancer / 临床检验杂志

Objective@#To investigate the degree of infiltration and distribution of tissue-resident CD8 + T cells (CD103 + CD8 + T cells) in gastric cancer tissues, and analyze the relationship between the degree of infiltration and clinicopathological features and prognosis. @*Methods@#Tissue microarray and immunofluorescence staining were used to examine the CD8 + T cells and CD103 + CD8 + T cells infiltration in 90 cases of gastric cancer and their adjacent normal tissues. Wilcoxon rank test was used to compare the CD8 + T cells, CD103 + CD8 + T cells infiltration and CD103 + CD8 + T cells/CD8 + T cells ratio in gastric cancer and corresponding normal tissues. The chi-square test was used to analyze the relationship between CD8 + T cells, CD103 + CD8 + T cells infiltration and CD103 + CD8 + T cells/ CD8 + T cells ratio in gastric cancer tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to explore the correlation between CD8 + T cells, CD103 + CD8 + T cells infiltration and CD103 + CD8 + T cells/ CD8 + T cells ratio and overall survival. Cox model was used to analyze the correlation between different clinical parameters and prognosis of the patients. @*Results@#There was no significant difference for the infiltration of CD103 + CD8 + T cells between the gastric cancer tissues and adjacent normal tissues (P＞0.05). The infiltration rate of CD103 + CD8 + T cells in the cases in stage Ⅲ to Ⅳ (69.09%, 38/55) was significantly lower than that in the stage Ⅰ to Ⅱ cases (91.43%, 32/35), (χ 2 =6.175, P=0.013). There was no significant correlation between CD103 + CD8 + T cells infiltration and other clinicopathological features (P＞0.05). Kaplan-Meier survival analysis showed that the patients with high CD103 + CD8 + T cells infiltration showed significantly longer overall survival than the patients with low CD103 + CD8 + T cells infiltration (HR=2.187, 95%CI: 1.062-4.500, P=0.033 6). Multivariate Cox model analysis indicated that tumor diameter (HR=2.031, 95%CI: 1.163-3.546, P=0.013) and CD103 + CD8 + T cells infiltration (HR=0.516, 95%CI: 0.285-0.934, P=0.029) were independent prognostic factors for gastric cancer. @*Conclusion@#CD103 + CD8 + T cells in gastric cancer tissues should be associated with good prognosis, suggesting that they play an important role in the inhibition of gastric carcinogenesis and development, and can be used as an important factor for the prognosis evaluation of the patients with gastric cancer.

Distribution of CD103+CD8+T cell infiltration in colorectal cancer tissues and its clinical significance / 中国肿瘤生物治疗杂志

@#Objective: To investigate the degree and distribution of tissue-resident CD8+ T cell (CD103+CD8+T cells) infiltration in colorectal cancer (CRC) tissues, and to analyze its relationship to patients’clinicopathological features and prognosis. Methods: Tissue chips of 88 cases of colon cancer tissues (No.HColA180Su14) and 77 cases of rectal cancer tissues (No. HRec-Ade180Sur-03) were obtained from Shanghai Outdo Biotech Co.,Ltd. Immunofluorescence staining was performed to examine the infiltration pattern and degree of CD103+CD8+T cells in the collected CRC tissues and their para-cancerous tissues. Wilcoxon rank test was used to compare CD103+CD8+T cell infiltration degree in CRC tissues and the para-cancerous tissues. Chi-square test was used to analyze the relationship between CD103+CD8+T cell infiltration in CRC and patients’clinicopathological features. Kaplan-Meier survival analysis was conducted to explore the correlation between CD103+CD8+T cell infiltration and patients’prognosis. Cox model was applied to analyze the correlation between different clinical parameters and patients’prognosis. Results: CD103+CD8+T cell infiltration presented no signifi ·cant differences between CRC and para-cancer tissues (P>0.05). Patients with distant metastasis had significantly lower CD103+CD8+T cell infiltration rate than patients without distant metastasis (P<0.01). There was no significant correlation between the infiltration of CD103+CD8+T cells and other clinicopathological features (P>0.05). Kaplan-Meier survival analysis showed that the overall survival (OS) of patients with high CD103+CD8+T cell infiltration was significantly longer than that of the patients with low infiltration (54.42% vs 25.00%, P<0.05). Multivariate Cox model analysis indicated that pathological grade (P<0.01) and high CD103+CD8+T cell infiltration (P<0.05) were independent prognostic factors for CRC. Conclusion： ：CD103+CD8+T cell infiltration in CRC is associated with patients’prognosis, suggesting that CD103+CD8+T cell plays an important role in the initiation and development of CRC.

3,3'-Diindolylmethane Inhibits Flt3L/GM-CSF-induced-bone Marrow-derived CD103+ Dendritic Cell Differentiation Regulating Phosphorylation of STAT3 and STAT5

The intestinal immune system maintains oral tolerance to harmless antigens or nutrients. One mechanism of oral tolerance is mediated by regulatory T cell (Treg)s, of which differentiation is regulated by a subset of dendritic cell (DC)s, primarily CD103+ DCs. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating immunity. The intestines are exposed to various AhR ligands, including endogenous metabolites and phytochemicals. It was previously reported that AhR activation induced tolerogenic DCs in mice or in cultures of bone marrow-derived DCs. However, given the variety of tolerogenic DCs, which type of tolerogenic DCs is regulated by AhR remains unknown. In this study, we found that AhR ligand 3,3'-diindolylmethane (DIM) inhibited the development of CD103+ DCs from mouse bone marrow cells stimulated with Flt3L and GM-CSF. DIM interfered with phosphorylation of STAT3 and STAT5 inhibiting the expression of genes, including Id2, E2-2, IDO-1, and Aldh1a2, which are associated with DC differentiation and functions. Finally, DIM suppressed the ability of CD103+ DCs to induce Foxp3+ Tregs.

CD103 molecule-mediated pancreatic islet allograft injury induced by CD8 T cells / 中华器官移植杂志

Objective To test whether the CD103 molecule mediates CD8+ T lymphocytes on allogeneic islet graft immune injury. Methods By using flow cytometry, the expression of CD103 in peripheral CD8+ T lymphocytes in wild-type C57BL/6 mice was detected. Allogenic islet transplantation models were made using Balb/c donor mice and C57BL/6 recipient mice. Recipients were divided into 3 groups: M290-SAP-treated mice were injected with CD103 immunotoxin M290-SAP; M290-treated mice were injected with CD103 monoclonal antibody M290; untreated mice were only transplanted islet without any drug treatment. CD3, CD8, CD44 and CD103 positive cells were counted in islet allograft infiltrative lymphocytes. CD3, CD8, and CD103 positive cells were measured in the mesenteric lymph node. The islet allografts were removed and subjected to HE staining and immunohistochemical staining at the time of graft loss or the end of the observation period. Results 44. 06% peripheral CD8+ T cells expressed CD103 in wild-type C57BL/6 mice. 29 % CD8+ T cells expressed CD103 in the infiltrative lyrnphocytes of islet allografts in the untreated mice. In M290-SAP-treated mice, the lymphocytes had no CD103 expression and the absolute number of CD8+ lymphocytes was decreased as well The blood glucose was maintained stable for more than 100 days (13 days in untreated group, P＜0.05) in the M290-SAP-treated mice. Moreover, the transplanted islets retained intact. Conclusion CD103 expression is required for destruction of pancreatic islet allograft by CD8+ T cells. CD103 might provide a novel target for therapeutic intervention in islet allograft rejection.