Prognostic significance of CD45RO+ memory T cell in human gastric cancer

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 262 Memory T cells survive for many months and years and are critically important for host defence in humans. In tumor immunity, they have been also suggested to play a significant role in tumor progression and metastasis. However, the clinical importance of memory T cells in actual human cancer remains largely unknown. In this study, we tried to reveal the clinical significance of tumor-infiltrating CD45RO+ memory T cells in human gastric cancer. We examined 89 gastric cancer patients who underwent surgery in our department. The median age of the patients was 65 years, with a range of 31 to 84 years. Sixty-three patients were male and 26 were female. Histopathological and clinical findings were scored according to the UICC-TNM classification. Twenty-eight patients were early gastric cancer (T1) and 61 were advanced gastric cancer (over T2). In addition, 44 patients had lymph node metastasis and 9 patients had distant metastasis. We performed immunohistochemistry on gastric cancer tissues and counted the cells stained positively for CD45RO+ infiltrating into cancer tissue. The mean number of positively stained cells was 133 (range: 39-216). Then we defined 46 patients with high density of CD45RO+ T cells as CD45RO+hi (more than 133 positive cells per HPF) and 43 patients with low density of CD45RO+ T cells as CD45RO+lo (fewer than 133 positive cells per HPF). Interestingly, CD45RO+hi patients had a tendency to have a better prognosis than CD45RO+lo patients (1-year survival rate; 92.6% vs 88.9%, 3-year survival; 79.5% vs 74.1%, 5-year survival; 76.5% vs 59.5%, respectively). In advanced tumors (over T2), there were significant differences in postoperative overall survival and disease-free survival rates between CD45RO+hi and CD45RO+lo patients with gastric cancer (P=0.019 in overall survival rate: 1-year survival rate; 89.8% vs 82.8%, 3-year survival; 75.4% vs 59.1%, 5-year survival; 71.4% vs 40.9%, respectively; P=0.015 in disease-free survival rate: 1-year survival rate; 72.7% vs 57.9%, 3-year survival; 68.7% vs 41.1%, 5-year survival; 64.6% vs 29.9%, respectively). Further analysis in advanced tumors revealed that there were significant correlations of CD45RO status with depth of tumor invasion (P=0.029, T2: 27, 87.1%, T3: 4, 12.9%, and T4: 0, 0% in 31 CD45RO+hi tumors versus T2: 18, 60.0%, T3: 8, 26.7%, and T4: 4, 13.3% in 30 CD45RO+lo tumors), positive lymphatic vessel invasion (P=0.045, 20 of 31, 64.5% CD45RO+hi versus 26 of 30, 86.7% CD45RO+lo), and pathological stage (P=0.049, stage I: 11, 35.5%, stage II: 11, 35.5%, stage III: 7, 22.6%, and stage IV: 2, 6.5% in 31 CD45RO+hi versus stage I: 7, 23.3%, stage II: 10, 33.3%, stage III: 3, 10.0%, and stage IV: 10, 33.3%). In conclusion, we have demonstrated for the first time that CD45RO+ memory T cell has a significant prognostic value in human gastric cancer, and also our data suggested that adaptive immune response is functionally critical in human gastric cancer.