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Titolo:
Low prevalence of selective human leukocyte antigen (HLA)-A and HLA-B epitope losses in early-passage tumor cell lines
Autore:
Giacomini, P; Giorda, E; Fraioli, R; Nicotra, MR; Vitale, N; Setini, A; Delfino, L; Morabito, A; Benevolo, M; Venturo, I; Mottolese, M; Ferrara, GB; Natali, PG;
Indirizzi:
Ist Regina Elena CRS, Immunol Lab, I-00158 Rome, Italy Ist Regina Elena CRS Rome Italy I-00158 Immunol Lab, I-00158 Rome, Italy Natl Res Council, Inst Biomed Technol, I-00162 Rome, Italy Natl Res Council Rome Italy I-00162 Biomed Technol, I-00162 Rome, Italy Natl Canc Inst, Immunogenet Lab, Ctr Adv Biotechnol, I-16132 Genoa, Italy Natl Canc Inst Genoa Italy I-16132 Adv Biotechnol, I-16132 Genoa, Italy Regina Elena Canc Inst, Pathol Lab, I-00162 Rome, Italy Regina Elena Canc Inst Rome Italy I-00162 athol Lab, I-00162 Rome, Italy
Titolo Testata:
CANCER RESEARCH
fascicolo: 11, volume: 59, anno: 1999,
pagine: 2657 - 2667
SICI:
0008-5472(19990601)59:11<2657:LPOSHL>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLASS-I PHENOTYPES; HUMAN SOLID TUMORS; MHC CLASS-I; MONOCLONAL-ANTIBODIES; MELANOMA-CELLS; HEAVY-CHAINS; INTRALOCUS DETERMINANT; LOCUS PRODUCTS; MESSENGER-RNA; C-MYC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Giacomini, P Ist Regina Elena CRS, Immunol Lab, Via Messi Oro 156, I-00158Rome, Italy Ist Regina Elena CRS Via Messi Oro 156 Rome Italy I-00158 ly
Citazione:
P. Giacomini et al., "Low prevalence of selective human leukocyte antigen (HLA)-A and HLA-B epitope losses in early-passage tumor cell lines", CANCER RES, 59(11), 1999, pp. 2657-2667

Abstract

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 carcinomatumors. Early-passage tumor cell lines were established in culture from the corresponding metastatic tumor lesions obtained in each patient. Both thecell lines and the tumor Lesions were compared, in their HLA-A and -B expression, to the peripheral blood mononuclear cells (PBMCs) obtained from thesame 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 HLAexpression 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 recognitionby CTLs and natural killer cells bearing activatory and inhibitory receptors for HLA-A, HLA-B, HLA-C molecules.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 06:22:51