The Expressions And Clinical Significance Of 4-1BB And 4-1BBL In Gastric Cancer And Blood

Objective: Gastric cancer is one of the most common malignant tumour in the world.The human anti-tumor immune almost is cellular immunity by T cell mediated and the activation of T cell needs bisignal stimulation: the first signal is provided by the compound of TCR combined MHC; the second signal is provided by costimulatories on the APC and the corresponding ligands on T cell. Only when stimulated by two signals specific T cell can be activated to take cell immunity and kill tumor cell.Besides CD28/B7, 4-1BB/4-1BBL is a pair of important costimulatory signal, which play svarious roles on cell-to-cell interaction, cell adhesiveness, antigen present, Tcell costimulation and signal transmission. 4-1BB is exists on the cell membrane superficial, and it expresses on activated T cell, monocyt, granulocyte and dendrite cell. Its ligand 4-1BBL exists on the cell membrane superficial.It expresses CD3 monoclonal antibody activated CD4+T cell clone PL11,EBV transfected B cell line MP1,monocyte line THP1 and MOTE, neuroblastoma SKNSH, brain, placenta, lung, bone, heart, liver, pancreas.This study we detected the expressions of 4-1BBL and 4-1BBL in gastric cancer and peri-cancer tissues and per-blood with flow cytometry,to approach the relationship between expression of it and the immunity in gastric cancer.Methods: 60 gastric cancer patients who were hospitalized from July to November of 2007 were selected. The the protein expressions of 4-1BB,4-1BBL,CD4+T,CD8T,NK cells were detected by flow cytometry in the human tissues of gastric cancer, and peri-cancer gastric mucosa , lymph cell, peripheral blood and lymph nodes.Results:1 Distribution of T cell subgroup and NK cell in gastric cancer and peripheral bloodThe ratio of CD3+,CD4+,CD8+,CD4+/CD8+ and NK cell in gastric cancer tissue were 33.90±9.78,37.44±8.90,36.40±8.86,0.51±0.11,9.28±3.37 respectively; the ratio of CD3+,CD4+,CD8+,CD4+/CD8+ and NK cell in peripheral blood were 58.90±10.85,52.01±9.55,20.66±5.19,1.57±0.49,19.94±6.28 respectively. Their ratio of CD3+,CD4+,CD4+/CD8+ and NK cell in gastric cancer were lower than them in peripheral blood respectively, the differences were statistically significant(P<0.05). The ratio of CD8+ T cell were higher in gastric cancer than it in peripheral blood, the differences were statistically significant (P<0.05).2 The 4-1BB protein expressions were mononuclear cells(1.0971±0.067) gastric cancer(1.0309±0.061), lymph nodes (0.9962±0.102) gastric mucosa(0.9788±0.161)and peripheral blood mononuclear cells (0.7876±0.170), in the sequence of from high to low. The expressions of 4-1BB protein in peripheral blood monouclear cells were lower than those of other tissues (P<0.05); and the expressions of 4-1BB protein in gastric cancer tissues were higher than gastric mucosa tissues (P<0.05). There was statistics difference.3 The expressions of 4-1BBL protein in gastric cancer (0.9754±0.073) were lower than gastric mucosa (1.0106±0.038), there was statistics difference (P<0.05).4 There were positive correlation between the expression of 4-1BB and the CD4+/CD8+,NK cells in gastric cancer tissue and there were positive correlation between the expression of 4-1BBL and the CD4+,CD8+,NK cells in gastric cancer tissue ,these were statistics difference (P<0.05).5.1 The expressions of 4-1BB protein in poorly differentiated pathology stages group (1.256±0.11).in moderately group (1.021±0.06), 4-1BBL in poorly differentiated pathology stages group (0.904±0.06).in moderately group (1.127±0.08), there were statistics difference (P<0.05).5.2 The expressions of 4-1BB protein in non-metastasis group (0.931±0.11), in metastasis group (1.164±0.06),4-1BBL in non-metastasis group (1.074±0.08),in metastasis group (0.924±0.07) there were statistics difference (P<0.05).5.3 The expression of 4-1BB in stageⅢ-Ⅳgroup were (1.002±0.06, 1.014±0.05) in stageⅠ-Ⅱgroup (1.276±0.07, 0.961±0.08) , 4-1BBL in stageⅢ-Ⅳ(1.014±0.05) in stageⅠ-Ⅱgroup (0.961±0.08) there were statistics difference (P<0.05). 5.4 The expression of 4-1BB/4-1BBL hadn't relation with the age, gender, tumor volume and invasion depth (P>0.05).Conclusion:1 The ratio of NK cell and CD4+/CD8+ in gastric cancer tissue are lower than them in peripheral blood respectively,which indicate gastric cancer tissue in low immunization.2 The costimulatory molecules 4-1BB are significantly higher in gastric cancer tissue than in gastric mucosa, which indicates the costimulatory molecules 4-1BB do against to part tumor reaction.3 The expression of 4-1BBL in gastric cancer tissue are lower than them in gastric mucosa, There is positive correlation between the ratio of NK cell, CD4+/CD8+cells and the expression of 4-1BBL in gastric cancer tissue, indicate gastric cancer tissue in low immunization relates to deficiency of 4-1BBL .4 The costimulatory molecules4-1BB are significantly deficiency in gastric cancer tissue mononuclear cells than in peripheral blood mononuclear cells, which indicates 4-1BB freebacking raise up, immune status in all of the body is lower than in part of gastric cancer tissue.5 There was an obviously relation between 4-1BB/4-1BBL and pathology type, TNM stage, indicating that the higher expression of 4-1BB/4-1BBL, the carcinogenesis, development of gastric carcinoma are severe. In a word, the immune escape and immune status in low of gastric cancer relate to disequilibrium expressions of 4-1BB/4-1BBL protein in the gastric cancer tissue. The expressions of 4-1BB are significantly higher in gastric cancer tissue, which it may do against to tumor reaction, but the absence expressions of 4-1BBL, wich it do not mediate lymph cell activation to do against to tumor reaction.