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

Turrini R, Merlo A, Dolcetti R, Zanovello P, Rosato A - Cancer Immunol. Immunother. (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology and Surgical Sciences, University of Padova, Italy.

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.

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Related in: MedlinePlus

a HLA-I, β2-microglobulin (b2m), and HLA-II percentage of positivity and MFI of expression on different T cell lines after i.p. and s.c. recovery. White and black bars refer to i.p. and s.c. injection, respectively, while gray bars refer to the in vitro condition. The percentage of positivity for in vitro markers expression is not shown and is always 100%. Figure shows mean ± SD of at least 3 independent experiments for each cell line. b Cytofluorimetric analysis of different epithelial tumor cell lines. Bars as in a. Figure shows mean ± SD of at least 3 independent experiments for each cell line
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Fig2: a HLA-I, β2-microglobulin (b2m), and HLA-II percentage of positivity and MFI of expression on different T cell lines after i.p. and s.c. recovery. White and black bars refer to i.p. and s.c. injection, respectively, while gray bars refer to the in vitro condition. The percentage of positivity for in vitro markers expression is not shown and is always 100%. Figure shows mean ± SD of at least 3 independent experiments for each cell line. b Cytofluorimetric analysis of different epithelial tumor cell lines. Bars as in a. Figure shows mean ± SD of at least 3 independent experiments for each cell line

Mentions: When T cells were considered (Fig. 2a), it turned out that the s.c. injection induced the partial down-modulation of MHC-I on all the lines we studied, except MOLT-3. The i.p. inoculation route affected marker expression on MOLT-3 and HuT-78 cells but did not influence Jurkat and CEM cell lines. Finally, two ovarian carcinoma and three malignant melanoma cell lines were tested: IGROV-1 and OVCAR-3 tumors strongly down-modulated HLA-I expression after either i.p. or s.c. injection, while all melanomas retained MHC-I expression when injected i.p. but lost it after s.c. administration. (Fig. 2b shows only SK23-Mel, as an example of the behavior of the three melanoma cell lines.) Again, also in the case of both T cell and epithelial tumor cell lines, data of pan MHC-I and MHC-II expression were confirmed by staining with anti-β2-microglobulin and allele-specific antibodies (Fig. 2a, b and data not shown).Fig. 2


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

Turrini R, Merlo A, Dolcetti R, Zanovello P, Rosato A - Cancer Immunol. Immunother. (2011)

a HLA-I, β2-microglobulin (b2m), and HLA-II percentage of positivity and MFI of expression on different T cell lines after i.p. and s.c. recovery. White and black bars refer to i.p. and s.c. injection, respectively, while gray bars refer to the in vitro condition. The percentage of positivity for in vitro markers expression is not shown and is always 100%. Figure shows mean ± SD of at least 3 independent experiments for each cell line. b Cytofluorimetric analysis of different epithelial tumor cell lines. Bars as in a. Figure shows mean ± SD of at least 3 independent experiments for each cell line
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3197938&req=5

Fig2: a HLA-I, β2-microglobulin (b2m), and HLA-II percentage of positivity and MFI of expression on different T cell lines after i.p. and s.c. recovery. White and black bars refer to i.p. and s.c. injection, respectively, while gray bars refer to the in vitro condition. The percentage of positivity for in vitro markers expression is not shown and is always 100%. Figure shows mean ± SD of at least 3 independent experiments for each cell line. b Cytofluorimetric analysis of different epithelial tumor cell lines. Bars as in a. Figure shows mean ± SD of at least 3 independent experiments for each cell line
Mentions: When T cells were considered (Fig. 2a), it turned out that the s.c. injection induced the partial down-modulation of MHC-I on all the lines we studied, except MOLT-3. The i.p. inoculation route affected marker expression on MOLT-3 and HuT-78 cells but did not influence Jurkat and CEM cell lines. Finally, two ovarian carcinoma and three malignant melanoma cell lines were tested: IGROV-1 and OVCAR-3 tumors strongly down-modulated HLA-I expression after either i.p. or s.c. injection, while all melanomas retained MHC-I expression when injected i.p. but lost it after s.c. administration. (Fig. 2b shows only SK23-Mel, as an example of the behavior of the three melanoma cell lines.) Again, also in the case of both T cell and epithelial tumor cell lines, data of pan MHC-I and MHC-II expression were confirmed by staining with anti-β2-microglobulin and allele-specific antibodies (Fig. 2a, b and data not shown).Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology and Surgical Sciences, University of Padova, Italy.

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.

Show MeSH
Related in: MedlinePlus