Research On Alteration And Function Of Peripheral Blood T-lymphocyte Subsets In Patients With Colorectal Cancer Peri-operation

PartⅠResearch on alteration and function of peripheral blood T-lymphocyte subsets in patients with colorectal cancer【Objective】: Detect alteration and function of peripheral blood T-lymphocyte subsets in patients with colorectal cancer and try to find out the mechanisms and influencing factors.【Methods】: 35 inpatients with colorectal cancer were operated in the first affiliated hospital of Soochow University from November 2005 to July 2006. 13 control outpatients were selected from people having medical examination without diseases at the same time. Differences were try to be found between the colorectal cancer patients and control cases in peripheral blood with CD3~+, CD4~+, CD8~+, CD4~+CD28~+, CD8~+CD28~+, CD4~+CD25~+, CD3~+CD56~+ T cell subsets and CD4/CD8 ratio. And we also gathered the clinical information of these patients and analyzed the changing mechanisms and influencing factors on those information.【Results】: There were no differences between colorectal cancer patients and the healthies'total lymphocytes and lymphocytes'centage account for peripheral white blood cell. Percentage of CD4~+CD28~+ T cell of peripheral blood in colorectal cancer patients was significantly higher than that of peripheral blood in control group (P<0.05). However, percentage of CD3~+CD56~+ T cell of peripheral blood in colorectal cancer patients was quite lower than that in control group (P<0.05). There were no differences between the colorectal cancer and control group patients'peripheral blood in CD3~+, CD4~+, CD8~+, CD8~+CD28~+, CD4~+CD25~+ T cells and CD4/CD8 ratio. Patients more than 60 years old had lower percentage of CD3~+ T cell and CD4~+CD28~+T cells (P<0.05, P=0.070), CD8~+, CD8~+CD28~+T in cases with limph nodes metastasis decreased significantly (P<0.05), CD3~+, CD4~+CD28~+ T cells had tendency to decline (P=0.066, 0.069). Patients with median tumor differentiation had lower CD3~+ T cell than patients with high and low tumor differentiation (P=0.073). CD8~+, CD8~+CD28~+, CD3~+CD56~+T cells decreased with tumor infiltration growing (P<0.05). CD3~+ T cell declined in those advanced Dukes stage patients (P<0.05). Sex, tumor position and size had no effect on T cell subsets. T cell subsets had linear regression relationship with age: CD3~+T cell reduced with cases age enhancing (linear regression equation: y=70.17-0.29x, r=0.302, P=0.093), CD4~+CD28~+ T cell also declined after age enhancing (linear regression equation: y=42.97-0.33x, r=0.370, P=0.031). T cell subsets even had linear regressions among themselves: CD4~+, CD4~+CD28~+T cells had the regression with CD3~+T cell (linear regression equations respectively: y=20.48~+0.28x, y=-8.70~+0.58x; r=0.373, 0.553; P=0.036, 0.001). And this relationship also happended between CD8~+, CD4~+CD28~+, CD4~+CD25~+T cells, CD4/CD8 ratio and CD4~+T cell (linear regression equations respectively: y=47.20-0.36x, y=2.72+0.56x, y=-0.79~+0.11x, y=-0.59+0.05x; r=0.366, 0.466, 0.362, 0.797; P=0.033, 0.0001, 0.006, 0.036); CD4/CD8 ratio, CD8~+CD28~+, CD3~+CD56~+T cells and CD8~+T cell (linear regression equations respectively: y=2.81-0.05x, y=-0.51+0.14x, y=-2.53+0.43x; r=0.755, 0.386, 0.346; P=0.0001, 0.024, 0.057);CD4~+CD25~+T cell and CD4/CD8 ratio (linear regression equation: y=-0.12+2.75x; r=0.534; P=0.001); CD8~+CD28~+T cell and CD4~+CD28~+T cell (linear regression equation: y=0.85~+0.14x; r=0.485; P=0.004).【Conclusions】: 1. Anti-tumor immune action mediated by T-lymphocyte subsets was suppressed in colorectal cancer patients. This immunosuppression surrounding was correlated highly with the patients'age, lymph node metastasis, tumor differentiation, tumor infiltration, Dukes stage and so on. Those patients with lymph node metastasis, bad tumor differentiation, infiltrated to chorion and outside of bowel, andvanced Dukes stages had less T-lymphocytes. 2. The action of T-lymphocyte subsets were affected by themselves. CD4~+, CD4~+CD28~+, CD8~+CD28~+, CD3~+CD56~+T cells could activate anti-tumor immune action, however, CD8~+, CD4~+CD25~+ T cells would suppress anti-tumor immune action. CD4/CD8 ratio increased when immune action activating. PartⅡResearch on alteration and influencing factors of peripheral blood T-lymphocyte subsets in patients with colorectal cancer peri-operation【Objective】: Detect alteration and function of T-lymphocyte subsets in patients with colorectal cancer post-operation 1 week and 1 month, and try to find out the mechanisms and influencing factors.【Methods】: Peripheral blood of 30 patients were taken from the first part of this experimental inpatients after 1 week post-operation, and another 15 samples were taken after 1 month after tumor resection in patients preparing to receive adjunct treatment. Differences were try to be found after tumor resection 1 week in peripheral blood with CD3~+, CD4~+, CD8~+, CD4~+CD28~+, CD8~+CD28~+, CD4~+CD25~+, CD3~+CD56~+ T cell subsets and CD4/CD8 ratio. And we also gathered the clinical information of patients and analyzed the changing mechanisms and influencing factors on the information.【Results】: Colorectal cancer patients have lower total lymphocytes and lymphocytes'centage account for peripheral white blood cells after cancer resection 1 week later than those of patients before resection and the healthies'(P<0.05). Colorectal cancer patients before cancer resection and after resection 1 month later have same total lymphocytes and lymphocytes'centage account for peripheral blood cells as the healthies. Percentage of CD4~+CD28~+T cell in colorectal cancer patients'peripheral blood increased significantly after tumor resection 1 week(P<0.05), and it nearly reached the percentage of control group's lever, but when to 1 month later, it declined to the lever before operation (P<0.05). There were no changes of CD8~+CD28~+T cell after resection 1 week, but it was lower than the control group (P=0.079), and recovered after resection 1 month. CD4~+CD25~+T cell hoisted after resection (P<0.05), and it was higher than the control group's, and till 1 month after operation it increased continuously. CD3~+CD56~+T cell has no change after operation (P>0.05), but keeping on a higher lever from 1 week to 1 month than the control group (P<0.05). There were no alterations after operation with CD3~+, CD4~+, CD8~+T cell and CD4/CD8 ratio. CD3~+, CD4~+CD28~+ T cells of female patients were higer than those of male patients after operation (P=0.101,0.068). Patients bellow 60 years old had more CD3~+T cell after resection (P=0.061). Colonic cancer patients had more CD3~+CD56~+T cell than rectal cancer patients after resection (P=0.035). Patients received allogeneic blood transfusion peri-operation had less CD4~+CD28~+ T cell than those patients without blood transfusion (P=0.052). CD8~+CD28~+ T cell decreased in patients who had corticosteroids dexamethasone injected during operation, while increased in patients had not dexamethasone injected. There were significant difference between the two groups (P=0.015); CD4~+CD25~+T cell increased in both of the two groups, but in patients had dexamethasone injected hoisted higher than cases had not after resection (P=0.008). Cases with lymph node metastasis had less CD3~+T cell (P=0.008). CD8~+ T cell decreased and CD4/CD8 ratio increased in cases with lymph node metastasis, however, CD8~+ T cell increased and CD4/CD8 ratio decreased in patients without lymph node metastasis after resection (P=0.012, 0.019). Patients with bad tumor differentiation tended to have more CD3~+CD56~+T cell after operation (P=0.066). Cases with tumor limited in muscle and mucous stratums had more CD8~+ T cell than tumor grew to chorion stratum till out of the bowel after resection (P=0.022). Moreover, CD3~+CD56~+T cell decreased in patients with tumor in muscle and mucous stratums while increased in patients with tumor in chorion stratum and/or out of the bowel after resection, as though patients with tumor in muscle and mucous stratums have more (P=0.012). CD3~+, CD8~+, CD4~+CD28~+ T cells and CD4/CD8 ration in cases with advanced stage in Dukes'C and D grew up more than in Dukes'A and B after resection, but patients with Dukes stage classification in A and B have more (P=0.097, 0.098).【Conclusions】: 1. Anti-tumor immune action mediated by CD4~+CD28~+, CD8~+CD28~+T cells fluctuated after resection 1 week to 1 month later in colorectal cancer patients with CD4~+CD28~+ T cell changing from activation to suppression and CD8~+CD28~+T cell from suppression to recover, while the action mediated by Treg, NKT cell keeping increasing. 2. The benefit effectors of the anti-tumor immune action mediated by T-lymphocyte subsets recovering after resection were female, young, well differentiation, infiltrated in lower stratum, colonic cancer, while the adverse effectors were lymph node metastasis, allogeneic blood transfusion, corticosteroids injuring.