Selective Changes in Expression of HLA Class I Polymorphic Determinants in Human Solid Tumors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 17; pp. 6719 - 6723
• Main Authors: Natali, P. G., Nicotra, M. R., Bigotti, A., Venturo, I., Marcenaro, L., Giacomini, P., Russo, C.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.09.1989; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; Adenocarcinoma; AMINO ACIDS; ANIMAL CELLS; ANIMAL TISSUES; ANTIBODIES; Antibodies, Monoclonal; ANTIGENS; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOCHEMISTRY; Biological and medical sciences; BIOLOGICAL MATERIALS; Biopsies; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CARBOXYLIC ACIDS; CELL TRANSFORMATIONS; CHEMISTRY; CONNECTIVE TISSUE CELLS; Cross Reactions; CYTOCHEMISTRY; DAYS LIVING RADIOISOTOPES; Determinants; DIGESTIVE SYSTEM; DRUGS; EPITHELIUM; Epitopes; EVEN-ODD NUCLEI; Female; FEMALE GENITALS; FLUORESCENCE; Fluorescent Antibody Technique; GASTROINTESTINAL TRACT; Genes, MHC Class I; GLANDS; Histocompatibility antigens class I; Histocompatibility Antigens Class I - analysis; Histocompatibility Antigens Class I - genetics; HLA antigens; Host-tumor relations. Immunology. Biological markers; Humans; Immunoenzyme Techniques; IMMUNOLOGY; INTESTINES; ISOTOPES; KIDNEYS; LARGE INTESTINE; LEUKOCYTES; LIGHT NUCLEI; LIPOTROPIC FACTORS; LUMINESCENCE; LYMPHOCYTES; Male; MALE GENITALS; MATERIALS; Medical sciences; MEMBRANE PROTEINS; METHIONINE; Molecules; MONOCLONAL ANTIBODIES; Neoplasms - immunology; Neoplasms - pathology; NUCLEI; ONCOGENIC TRANSFORMATIONS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; ORGANS; Polymorphism, Genetic; PROSTATE; PROTEINS; RADIOISOTOPES; Reactivity; RECEPTORS; RECTUM; SOMATIC CELLS; SULFUR 35; SULFUR ISOTOPES; TISSUES; TUMOR CELLS; Tumors; UTERUS; Human; HLA-System; Optical microscopy; Immunocytochemistry; Major histocompatibility system; Tumor; Monoclonal antibody; Immunofluorescence; Class I histocompatibility antigen
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.17.6719

Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. We have found that in HLA-A2-positive patients (identified by reactivity of their normal tissues with mAb BB7.2), HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue, skin, ovary, urinary bladder, prostate, and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B,C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. Immune surveillance to tumors is thought to depend on cytotoxic T cells, which require corecognition of polymorphic HLA class I epitopes, and on natural killer cells, which are, on the contrary, activated by the absence of HLA class I antigens. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance.