PMID- 10363989
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 11
DP  - 1999 Jun 1
TI  - Low prevalence of selective human leukocyte antigen (HLA)-A and HLA-B epitope 
      losses in early-passage tumor cell lines.
PG  - 2657-67
AB  - 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.
FAU - Giacomini, P
AU  - Giacomini P
AD  - Laboratory of Immunology Regina Elena Institute, Centro della Ricerca 
      Sperimentale, Rome, Italy. giacomini@crs.ifo.it
FAU - Giorda, E
AU  - Giorda E
FAU - Fraioli, R
AU  - Fraioli R
FAU - Nicotra, M R
AU  - Nicotra MR
FAU - Vitale, N
AU  - Vitale N
FAU - Setini, A
AU  - Setini A
FAU - Delfino, L
AU  - Delfino L
FAU - Morabito, A
AU  - Morabito A
FAU - Benevolo, M
AU  - Benevolo M
FAU - Venturo, I
AU  - Venturo I
FAU - Mottolese, M
AU  - Mottolese M
FAU - Ferrara, G B
AU  - Ferrara GB
FAU - Natali, P G
AU  - Natali PG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Antibody Specificity
MH  - *Down-Regulation
MH  - Epitopes/immunology/*metabolism
MH  - Flow Cytometry
MH  - Genotype
MH  - HLA-A Antigens/genetics/immunology/*metabolism
MH  - HLA-B Antigens/genetics/immunology/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunologic Surveillance
MH  - Neoplasms/*immunology
MH  - Polymorphism, Genetic
MH  - Tumor Cells, Cultured
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Jun 1;59(11):2657-67.