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

• Published in: Clinical cancer research 2006-01, Vol.12 (2), p.411-416
• Main Authors: OSHIKIRI, Taro, MIYAMOTO, Masaki, MORITA, Takayuki, FUJITA, Miyoshi, MIYASAKA, Yuji, SENMARU, Naoto, YAMADA, Hidehisa, TAKAHASHI, Toshiyuki, HORITA, Shoichi, KONDO, Satoshi
• Format: Article
• Language: English
• Subjects: 22-1-1 monoclonal antibody; Acetylgalactosamine - immunology; Antibodies, Monoclonal - immunology; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; CD8; CD8-Positive T-Lymphocytes - immunology; colorectal cancer; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Disease Progression; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunoenzyme Techniques; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Rate; T cells; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-1257

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