Background: Adoptively transferred interleukin-2 activated natural killer (A-NK) cells are capable of selectively infiltrating tumor, however, only at low efficiency. The aim of this study was to investigate the intratumoral A-NK cell retention using an ex-vivo tissue-isolated tumor preparation.
Methods: R3230AC mammary adenocarcinoma and CSE fibrosarcoma were implanted in the ovarian fat pad of Fisher 344 rats. The tumors were perfused ex vivo 14 to 15 days post-implant with a known number of fluorescent labelled A-NK cells, and the effluent collected serially over time. Non stimulated splenocytes (N-SS) were used as controls.
Results: In group 1, tumors were perfused with either A-NK (n = 16) or N-SS (n = 7) cells. The mean number of the cells which remained intratumorally at the completion of the perfusion was 48.37% +/- 14.94 for A-NK cells and 34.68% +/- 13.20 of N-SS (p = 0.048). In group 2, tumors were perfused with a suspension containing both A-NK and N-SS cell (n = 11). The difference in tumor retention between A-NK cells and N-SS was 22.5% (p = 0.0053) for R3230AC tumors (retention of intratumoral A-NK cells was 45.1% +/- 6.47 vs. 22.6% +/- 19.09 for N-SS) and 15.88% (p = 0.028) for the fibrosarcomas (34.01% +/- 15.96 vs. 18.12 +/- 17.78 for A-NK and N-SS, respectively). No difference with respect to retention of A-NK cells or N-SS cells was observed between tumor types (p = 0.23 and p = 0.71, respectively).
Conclusions: The retention of A-NK cells in tumor tissues was significantly better than the retention of N-SS when administered directly. Since the retention of A-NK cells in tumor tissue was high (35-50%), this factor does not explain the low efficiency of adoptively transferred A-NK cells accumulating in tumors when administered systemically.