Invariant chain expression in gastric cancer
Introduction
Intracytoplasmic invariant chain (Ii) protein is a chaperone molecule which regulates the function of HLA class II molecules [1], [2]. Ii protein regulates antigen presentation by HLA class II molecules by inhibiting their cytoplasmic form from binding to endogenously derived antigenic peptides. Recent work on the mechanisms involved in anti-tumor immune response has indicated that humoral mediators or abnormal expression of tumor-associated antigens result in low lymphocytic response against tumor cells [3], [4], [5]. It has been elucidated that Ii in cancer cells was one of the molecules related with immunosuppression [6]. Increased Ii expression in tumor cells inhibits tumor antigen presentation by HLA class II molecules, disrupting the HLA class II mediated immune stimulation by tumor cells [7]. Thus, Ii positive tumor cells may have a significant influence on tumor behavior.
Previous studies on HLA-DR expression in several cancers including gastric cancers revealed a positive relationship between Human Leukocyte Antigen-DR (HLA-DR) expression and prognosis of the disease [8], [9], [10]. However, clinicopathological characteristics correlated with Ii expression and its prognostic implication were not fully disclosed. We herein attempt to clarify, retrospectively, the clinicopathological features of Ii positive gastric cancer.
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Materials and methods
One hundred and twenty six patients who had undergone gastrectomy for gastric cancer between 1988 and 1995 at the First Department of Surgery, Kagoshima University School of Medicine were entered into this study. The mean age of the participants was 65.0 years (range 30–87), and the male /female ratio was 2.6 (91/35). One hundred and twelve patients received curative resection, while the remaining 14 underwent non-curative gastrectomy. A total of 60 patients received total gastrectomy, 51
Results
Both HLA-DR (Fig. 1) and Ii (Fig. 2) immunoreactivity was identified on the surface of the tumor cells. Some populations of tumor infiltrating lymphocytes were also immunopositive for those markers. Patients were divided into groups according to Ii or HLA-DR expression: 48 patients were placed in the Ii positive group, and 78 patients were placed in the Ii negative group. The HLA-DR positive group consisted of 46 patients while 80 patients were placed in the HLA-DR negative group.
Discussion
It has been suggested that increased Ii expression in tumor cells prevents presentation of tumor antigens by HLA class II molecules [6]. Poor antigen presentation to intratumoral T-cells may then weaken the host immune defense against tumor cells. There are few clinical studies on Ii expression in cancer patients [6], [12] and the results are not always similar, indicating the need for further investigation. This study describes Ii expression in gastric cancer and, for the first time, shows a
References (14)
- et al.
The role of IL-10 in crossregulation of TH1 and TH2 responses
Immunol. Today
(1991) - et al.
MHC class II antigen-associated invariant chain on renal cell cancer may contribute to the anti-tumor immune response of the host
Cancer Lett.
(1996) - et al.
Diversity of endogenous epitopes bound to MHC class II molecules limited to invariant chain
Science
(1994) - et al.
The function of invariant chain in class II-restricted antigen presentation
Semin. Immunol.
(1995) - et al.
Enhancement of antitumor immunity by CTLA-4 blockade
Science
(1996) - et al.
Alternations in signal transduction molecules in T lymphocytes from tumor-bearing mice
Science
(1992) - et al.
Invariant chain statement in colon neoplasms
Virchows Arch.
(1999)
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