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Prognostic Significance of Activated CD8⁺ T Cell Infiltrations within Esophageal Carcinomas

Department of Surgery and Surgical Oncology [K. S., P. M. S.], Division of Pathology [W. H.], Robert Rössle Hospital and Tumor Institute, Charité, Humboldt University of Berlin, and Max Delbrück Center for Molecular Medicine [K .S., C. R., P. M. S.], Berlin, Germany 13122

The purpose of this study was to explore whether there is a linkage between the infiltration of CD8⁺ T cells and the risk of death from esophageal cancer. Cases of 70 consecutive patients in whom esophageal squamous cell carcinomas ( n = 33) or adenocarcinomas (n = 37) were R0-resected between 1993 and 1999 were reviewed. The presence of activated CD8⁺ T cells was evaluated by quantitative real-time PCR and immunohistochemistry and compared to clinical and pathological stages. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. Intratumoral (i.t.) CD8⁺ T cells accumulating within the epithelial complexes were detected in 11 of all (16%) cases: in 9 of 25 (36%) patients with Union Internationale Contrele Cancer stage I or II versus 2 of 45 (4%) patients with Union Internationale Contrele Cancer stage III or IV (P = 0.001). Intratumoral CD8⁺ T cell infiltrations showed proliferative activity and also IFN- secretion. The presence of i.t. CD8⁺ T cell infiltration more than peritumoral infiltration was associated with a good prognosis in both squamous cell and adenocarcinomas. Multivariate analysis showed that i.t. CD8⁺ T cell infiltration was an independent prognostic factor (hazard ratio, 0.5; P = 0.0004) indicating favorable outcome. In conclusion, the presence of CD8⁺ T cell infiltration in esophageal carcinomas is a favorable prognostic factor that should have diagnostic and therapeutic implications.

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