This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giacomini, P. Articles by Natali, P. G. Search for Related Content PubMed PubMed Citation Articles by Giacomini, P. Articles by Natali, P. G.

Low Prevalence of Selective Human Leukocyte Antigen (HLA)-A and HLA-B Epitope Losses in Early-Passage Tumor Cell Lines¹

Laboratory of Immunology, Regina Elena Institute, Centro della Ricerca Sperimentale (CRS), 00158 Rome [P. G., E. G., R. F., M. R. N., N. V., A. S., P. G. N.]; Institute of Biomedical Technology, National Research Council, 00162 Rome [M. R. N.]; Laboratory of Immunogenetics, National Cancer Institute, Center for Advanced Biotechnology, 16132 Genoa [L. D., A. M., G. B. F.]; Laboratory of Pathology, Regina Elena Cancer Institute, 00162 Rome [M. B., M. M.]; and Medical Oncology II, Regina Elena Institute, 00162 Rome [I. V.], Italy

The down-regulation of human leukocyte antigen (HLA) class I molecules, especially the selective down-regulation of certain allelic products, is believed to represent a major mechanism of tumor escape from immune surveillance. In the present report, an original approach is described to precisely evaluate and classify HLA class I epitope losses in 30 cancer patients with malignant melanoma and lung, breast, endometrium, ovary, and colon carcinoma tumors. Early-passage tumor cell lines were established in culture from the corresponding metastatic tumor lesions obtained in each patient. Both the cell lines and the tumor lesions were compared, in their HLA-A and -B expression, to the peripheral blood mononuclear cells (PBMCs) obtained from the same patient (autologous PBMCs). On the basis of HLA-genotyping data, the appropriate monoclonal antibodies identifying mono- and poly-morphic HLA-A and HLA-B epitopes were selected from a panel of 34 antibodies for a total of 24 testable alleles. The selected antibodies were used not only in immunohistochemical assays on cryostatic tumor sections and cytospins of PBMCs but also in quantitative, sensitive flow cytometry assays on early-passage tumor cells and PBMC suspensions. With this latter method, a low overall HLA expression was detected in 26 tumor cell explants and a complete, generalized HLA-A, HLA-B, HLA-C loss in the remaining 4 cases. However, no complete, selective loss of any of the 45 tested HLA-A and HLA-B allomorphs was observed. Sequences from all of the HLA class I alleles could be detected at the genomic DNA level in tumor cells and tissues. At variance from the literature and the results of immunohistochemical experiments performed in parallel on the corresponding tumor lesions, the relative proportions of the various HLA epitopes were relatively preserved in each early-passage cell line/PBMC pair, and selective increases, rather than decreases, in the expression of polymorphic HLA epitopes had the highest prevalence and greatest magnitude. Our data suggest an alternative tumor stealth strategy in which up- and down-regulation are equally important. This alternative model of tumor-host interaction better fits the available models of tumor cell recognition by CTLs and natural killer cells bearing activatory and inhibitory receptors for HLA-A, HLA-B, HLA-C molecules.

This article has been cited by other articles:

				E. Giorda, L. Sibilio, A. Martayan, S. Moretti, I. Venturo, M. Mottolese, G. B. Ferrara, S. Cappellacci, L. Eibenschutz, C. Catricala, et al. The Antigen Processing Machinery of Class I Human Leukocyte Antigens: Linked Patterns of Gene Expression in Neoplastic Cells Cancer Res., July 15, 2003; 63(14): 4119 - 4127. [Abstract] [Full Text] [PDF]

				G. Parmiani, C. Castelli, P. Dalerba, R. Mortarini, L. Rivoltini, F. M. Marincola, and A. Anichini Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going? J Natl Cancer Inst, June 5, 2002; 94(11): 805 - 818. [Abstract] [Full Text] [PDF]