Loss of monomorphic and polymorphic HLA antigens in metastatic breast and colon carcinoma

Abstract

Summary MHC class I antigens are intimately involved in intercellular communication, and recognition by cytotoxic T cells. Thus tumour cells that fail to express them may be at a growth or metastatic advantage. A series of ten colorectal and ten breast carcinomas, and their respective lymph node metastases, were examined immunohistologically using monoclonal antibodies (mAb) against both monomorphic and A2 polymorphic determinants, and beta-2-microglobulin (beta 2m). Four (Benacerraf, 1981;Linsk & Goodenow, 1986;Schwartz, 1982). The class I MHC molecule consists of three alpha regimes, covalently linked to beta-2-microglobulin (beta 2m), which are encoded by separate genes, and linked prior to expression at the cell membrane (Ploegh et al., 1981;Arce-Gomez, 1978 (Eisenbach et al., 1983;1985). Studies on the expression of human MHC class I antigens in primary vs metastatic tumour are limited; for example malignant melanoma, digestive tract, and laryngeal tumours (Ruiz-Cabello et al., 1989;Esteban et al., 1989). In these studies, both increased and decreased expression of monomorphic determinants of HLA class I was observed in the metastases compared with their primaries. In the present study we have used mAbs to evaluate a series of human primary colon and breast carcinomas, and their lymph node metastases, for the expression of monomorphic and polymorphic HLA class I determinants. Normal colon mucosa and, where possible, colon adenomas and liver metastases were included in the study. Many of the primary tumours at both sites showed reduced staining for monomorphic and polymorphic HLA class I determinants; metastases showed both greater and lesser degrees of loss of HLA expression when compared with their primary. Materials and methods Patients

Microarray analysis reveals potential mechanisms of BRMS1-mediated metastasis suppression

“…Previous studies have shown that some MHC class I genes are not expressed in certain cancers, which may alter the immune response [20][21][22]. Altered expression of MHC, class I and II molecules has been described in metastatic lesions from breast tumors [23][24][25] and breast cancer lines [26].…”

Ly49 Family Receptors Are Required for Cancer Immunosurveillance Mediated by Natural Killer Cells

“…Tumors evade immune recognition through various mechanisms, such as alteration of the tumor microenvironment or changes in MHC-I expression. Reduced or complete loss of MHC-I expression has been seen in a wide array of human cancers, including colorectal (13,14), breast (13,15), bladder (16), ovarian (17), and cervical carcinoma (18), suggesting the presence of immunoediting.…”

Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands

“…The cell killing actions of the adaptive immune response can be mitigated by the decreased expression of MHC molecules on cancer cells. [26][27][28] A more general resistance to immune cell killing may also be achieved by the increased expression of anti-apoptotic proteins, such as survivin and other IAPs, by cancer cells. 29,30 To obtain insight into cellular pathways that are associated with an increased resistance to immune cells, we screened a compound library for agents that sensitize colon cancer cells to TNF induced apoptosis, without affecting cell viability on their own.…”