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CD4⁺ and CD8⁺ T Cells Cooperate to Improve Prognosis of Patients with Esophageal Squamous Cell Carcinoma

Surgical Oncology, Cancer Medicine, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Hokkaido 060-8638, Japan [Y. C., M. M., K. K., A. F., T. Shic., Y. K., Y. H., T. O., T. K., M. S., Y. N., K. H., S. M., S. O., S. K., H. K.]; Department of Pathology, Teinekeijinkai Hospital, Hokkaido 006-0811, Japan [T. Shin.]; and Department of Pathology, Hokkaido University Hospital, Hokkaido 060-8648, Japan [T. I.]

The purpose of this study is to clarify the roles of immune cell types, both individually and synergistically, in esophageal squamous cell carcinoma (ESCC). One hundred and twenty-two patients (105 males and 17 females; mean age, 62.3 years) with primary ESCC underwent surgical tumor resection at the Department of Surgical Oncology, School of Medicine, Hokkaido University and two affiliated hospitals between 1989 and 1999. Immunohistochemical analyses were performed for CD4, CD8, and CD57 (surface markers for natural killer cells). Patient prognosis was found to correlate with the number of CD4⁺ and CD8⁺ T cells in the stroma and the number of CD8⁺ T cells within the cancer cell nest. Furthermore, the number of CD8⁺ T cells in the stroma and within the cancer cell nest was found to be correlated [correlation coefficient (r) = 0.790; P < 0.0001). However, no correlation was observed between the number of natural killer cells and patient prognosis. Patients were classified into the following four groups based on CD4⁺ and CD8⁺ T-cell count: CD4/8(+/+), CD4/8(+/-), CD4/8(-/+), CD4/8(-/-). For the general patient pool, as well as for selected p-stage III and IV cases (n = 48), the survival rate for CD4/8(+/+) patients was significantly higher than that for the other three groups (log-rank test, P = 0.0012 and 0.0088, respectively). Multivariate analysis identified CD4/8(+/+) status, T classification, and N classification as independent prognostic factors. In conclusion, cooperation between CD4⁺ and CD8⁺ T cells correlates strongly with ESCC patient prognosis.

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