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Inhibition of cancer cell immune evasion by combined application of cytotoxic T-lymphocytes and natural killer cells

Zhang Y*, Wang Y, Decker KW, Wang Z, Zimmerman M

Development of cancer is often dependent upon subversion of immune surveillance which can include alteration of MHC class I antigen expression to avoid recognition by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. CTL and NK cells recognize and destroy MHC class I positive and negative cancer cells, respectively. To determine whether selection pressure from CTL and/or NK cells can modulate MHC class I expression levels on cancer cells as well as to determine if combined application of CTL and NK cells can inhibit immune evasion of cancer cells, MHC class I antigen on cancer cells was examined by flow cytometry and cancer cell killing was evaluated by in vitro and in vivo cytotoxic assays. These exper-iments demonstrated that: 1) MHC class I antigen expression on any individual cancer cell can be highly variable, 2) the strength of MHC class I antigen expression on cancer cells can change during culture, 3) high levels of MHC class I expression mediated greater sensitivity to CTL killing whereas lower levels of MHC class I imparted greater sensitivity to NK cell killing, 4) immune selection pressure can actively modulate surface MHC class I expression, and 5) combined application of CTLs and NK cells mediated much more effective cancer cell cytotoxicity. These results suggest that combined application of CTLs and NK cells could significantly increase the efficiency of cancer cell killing by inhibiting positive and negative selection pressures.