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

Authors' Affiliations: Departments of ¹ Surgery, ² Pathology, and ³ Internal Medicine, Hokkaido Gastroenterology Hospital and ⁴ Surgical Oncology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan

Requests for reprints: Taro Oshikiri, Department of Surgery, Hokkaido Gastroenterology Hospital, Honcho 1jo, 1chome, Higashi, Sapporo, 065-0014, Japan. Phone: 81-11-784-1811; Fax: 81-11-784-1838; E-mail: tarotaro{at}yf7.so-net.ne.jp.

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.

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