Tumor-associated antigen recognized by the 22-1-1 monoclonal antibody encourages colorectal cancer progression under the scanty CD8+ T cells.
OBJECTIVE
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.


METHODS
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.
Oshikiri
Taro
T
Department of Surgery, Hokkaido Gastroenterology Hospital and Surgical Oncology, Hokkaido University Hospital, Honcho 1jo, 1chome, Higashi, Sapporo 065-0014, Hokkaido, Japan. tarotaro@yf7.so-net.ne.jp
Miyamoto
Masaki
M
Morita
Takayuki
T
Fujita
Miyoshi
M
Miyasaka
Yuji
Y
Senmaru
Naoto
N
Yamada
Hidehisa
H
Takahashi
Toshiyuki
T
Horita
Shoichi
S
Kondo
Satoshi
S
D000116:Acetylgalactosamine / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
C099099:22-1-1 antigen; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000116:Acetylgalactosamine