Retention of adoptively transferred interleukin-2-activated natural killer cells in tumor tissue

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.

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.

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).

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.