Differential down-modulation of HLA class i and II molecule expression on human tumor cell lines upon in vivo transfer

Riccardo Turrini, Anna Merlo, Riccardo Dolcetti, Paola Zanovello, Antonio Rosato

Research output: Contribution to journalArticle

Abstract

Previous evidence from our laboratory showed that Epstein-Barr virus-immortalized lymphoblastoid B cells undergo a prominent down-modulation of HLA-II molecule expression when injected intraperitoneally in SCID mice, while HLA-I remains almost unaffected. Since this phenomenon can alter the experimental outcome of therapeutic protocols of adoptive cell therapy, we decided to evaluate the behavior of MHC antigens in a panel of cell lines belonging to the B- and T-cell lineages, as well as in epithelial tumor cell lines. Cells were administered in mice either intraperitoneally or subcutaneously and recovered 4 days later for HLA molecule expression analysis. Collected data showed a highly heterogeneous in vivo behavior of the various cell lines, which could alternatively down-modulate, completely abrogate or maintain unchanged the expression of either MHC-I or MHC-II molecules. Moreover, the site of injection impacted differentially on these aspects. Although such phenomena still lack a comprehensive clarification, epigenetic mechanisms are likely to be involved as epigenetic drugs could partially counteract MHC down-modulation in vivo. Nonetheless, it has to be pointed out that careful attention must be paid to the assessment of therapeutic efficacy of translational protocols of adoptive immunotherapy, as modulation of MHC molecules on human target cells when transferred in a mouse environment could readily interfere with the desired and expected therapeutic effects.

Original languageEnglish
Pages (from-to)1639-1645
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume60
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Down-modulation
  • HLA-I
  • HLA-II
  • Mouse model

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'Differential down-modulation of HLA class i and II molecule expression on human tumor cell lines upon in vivo transfer'. Together they form a unique fingerprint.

  • Cite this