Invariant chain expression in colon neoplasms

Abstract

Invariant chain (Ii) is a chaperone molecule that inhibits binding of endogenous antigens to class II molecules. High levels of Ii in cancer cells may prevent tumour antigen expression with class II and render the tumour less immunogenic. To correlate the expression of Ii and class II molecules in colon carcinomas with the density of tumour infiltrating lymphocytes (TILs), surgical specimens from a total of 48 patients with well-(WDAC), moderately (MDAC) and poorly differentiated adenocarcinomas (PDAC), adenoma with high-grade dysplasia (AdHGD) and adenomas were immunostained for Ii and class II antigen (HLA-DR). Aggregates of TILs were graded in H&E-stained sections. Normal colon epithelium was negative for Ii and HLA-DR. Invasive carcinomas showed a linear increase in the expression of Ii in the progression from low- to high-grade tumours, while there was no significant difference in HLA-DR expression across the groups. Invasive carcinomas showed a disproportionate increase in Ii over HLA-DR. Frequency of TILs showed inverse correlation with expression of Ii and tumour grade. This is the first demonstration that expression of Ii increases in the progression from low- to high-grade colon neoplasms and is most marked in the poorly differentiated carcinomas. Ii expression by carcinomas is inversely related to the frequency of TILs. The findings suggest that increased Ii renders the tumour less immunogenic and less likely to stimulate a host immune response.

CD74 Is Expressed by Multiple Myeloma and Is a Promising Target for Therapy

“…It was then shown that the aggressive in vivo behavior of this cell line could be restored by increasing CD74 levels by transfection (30). An association between pathological dedifferentiation, aggressive clinical behavior, and CD74 expression also has been observed in colon cancer specimens (31). The CD74ϩ/DRϪ phenotype observed in the multiple myeloma cases we studied may have similar implications for the biology of multiple myeloma.…”

Expression of Invariant Chain (CD 74) and Major Histocompatibility Complex (MHC) Class II Antigens in the Human Fetus1

“…It should be noted that, within the colon, altered expression of MHC and Ii/CD74 has been noted in the vicinity of tumors (Degener et al 1988). A significant number of tumors also exhibit non-coordinate expression with greater amounts of Ii/CD74 than MHC II (Degener et al 1988;Moller et al 1991;Jiang et al 1999). Jiang et al (1999) have demonstrated an association of increased Ii/CD74 expression and poor-grade and intratumoral lymphocytes.…”

“…A significant number of tumors also exhibit non-coordinate expression with greater amounts of Ii/CD74 than MHC II (Degener et al 1988;Moller et al 1991;Jiang et al 1999). Jiang et al (1999) have demonstrated an association of increased Ii/CD74 expression and poor-grade and intratumoral lymphocytes. On the basis of this finding they suggest that excess Ii/CD74 expression might render the tumor less immunogenic by inhibiting antigen presentation.…”

Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression

“…40 CD74, a transmembrane glycoprotein, acts as a chaperone molecule suppressing immune response by inhibiting the cytoplasmic form of HLA class II molecules from binding to endogenously derived antigen peptides. 25 The overexpression of CD74 has been observed in gastric cancer, 41 colonic adenocarcinoma, 42 melanoma, 43 renal epithelial neoplasms 44 and thymic epithelial neoplasms. 45 These findings have led to the proposal that tumors use CD74 as a mechanism to escape the host immune response.…”