Influence of LAK cells on expression of HLA-DR antigen on laryngeal carcinoma cell line in new culture systems.

We demonstrated the enhancement of HLA-DR antigen expression on cultured laryngeal carcinoma cells (Hep 2) by in vitro cultivation with LAK cells using flow cytometric and immunohistological analysis. For in vitro cultivation of tumor cells with LAK cells, we used newly developed experimental systems (the Transwell double-dish system and experimental three-dimensional tumors). In flow cytometric analysis, expression of HLA-DR antigen on tumor cells was compared before and after co-cultivation with LAK cells. When tumor cells were cultured separately with LAK cells in a Transwell Petri dish and the expression of HLA-DR antigen on tumor cells was analyzed by flow cytometry, the expression of HLA-DR antigen on tumor cells was increased in a dose-dependent manner related to the number of LAK cells used. Furthermore, when anti-interferon-gamma monoclonal antibody was added to the experimental system, enhancement of HLA-DR antigen expression was blocked. These findings were consistent with immunohistological studies, in which experimental three-dimensional Hep 2 cell tumors were established in double-layered agar with/without being co-cultivated with LAK cells. The expression of HLA-DR antigen in this system was significantly increased when compared to such expression before cultivation with LAK cells. These findings suggested that the culture systems employed in this study could be a possible model for examining solid tumor in vivo biological responses. This enhanced expression of HLA-DR antigen may also represent one of the multi-factorial responses seen with adoptive LAK cell immunotherapy for solid tumors.