Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

Abstract

PURPOSE: The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a novel tumor-associated antigen. Although evidence suggests that RCAS1 suppresses immunity by inducing tumor-infiltrating lymphocyte (TIL) apoptosis, RCAS1 function in humans is controversial. RCAS1 overexpression leads to the generation of the Tn glycan antigen (N-acetyl-D-galactosamine, GalNAc) recognized by the 22-1-1 monoclonal antibody. The objective of this study is to examine Tn glycan antigen function in colorectal cancer and to determine its relationship to CD8+ T cells and prognosis. EXPERIMENTAL DESIGN: Immunohistochemical analyses examined Tn expression in tumor cells and CD8 on TILs in 146 surgically resected colorectal cancer. RESULTS: Of 146 samples, 68 tumors (47%) were Tn+; 72 tumors (49%) were CD8+. Using Cox multivariate analysis and the Kaplan-Meier method, Tn and CD8 positivity were determined to be mutually independent prognostic factors (P = 0.0266 and 0.0210, respectively). Tn+ patients with CD8+ TILs exhibited better survival than Tn+/CD8- patients (P = 0.0129). For CD8- patients, Tn positivity was associated with decreased survival from that seen in Tn- patients (P = 0.0097), suggesting that Tn exerts a function independent of CD8+ T cells in tumor progression. In all patients and cases with synchronous liver metastases (n = 29), the Tn+/CD8- survival rate was significantly lower than that seen for other groups (P = 0.0001 and 0.0063, respectively). The average number of liver metastases in Tn+/CD8- cases also increased (mean, 8.2 tumors; P = 0.0032). Multivariate analysis identified Tn+/CD8- status and Dukes' staging as independent prognostic factors (P = 0.0016 and < 0.0001, respectively). CONCLUSIONS: Tn may encourage invasion and innidiation through a mechanism independent of CD8+ T cells. Thus, Tn+/CD8- status is a risk factor for multiple liver metastases development and an independent negative prognostic factor for colorectal cancer.