Selective changes in expression of HLA class I polymorphic determinants in human solid tumors.
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.
Natali
P G
PG
Department of Immunology, Regina Elena Cancer Institute, Rome, Italy.
Nicotra
M R
MR
Bigotti
A
A
Venturo
I
I
Marcenaro
L
L
Giacomini
P
P
Russo
C
C
D000911:Antibodies, Monoclonal; D003429:Cross Reactions; D005260:Female; D005455:Fluorescent Antibody Technique; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011110:Polymorphism, Genetic
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I