Selective changes in expression of HLA class I polymorphic determinants in human solid tumors

P. G. Natali, M. R. Nicotra, A. Bigotti, I. Venturo, L. Marcenaro, P. Giacomini, C. Russo

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)6719-6723
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number17
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Dive into the research topics of 'Selective changes in expression of HLA class I polymorphic determinants in human solid tumors'. Together they form a unique fingerprint.

Cite this