Modulating the antitumor immunity of MBT-2 murine bladder tumor bearing mice by postoperative administration of interferon-alpha

This study was conducted mainly to investigate the effect of interferon-a ( IFN-a) on the antitumor immunity of a tumor bearing host (TBH) when postope ratively administrated with or without lethally irradiated autologous tumor cells. Using the C3H/He-MBT-2 murine bladder tumor model, a status of post operative residual tumor was mimicked by rechallenging tumor cells 24 hours after resecting the day-17 tumor. Using immunohistochemical analysis we de monstrated that after treating with lethally irradiated MBT-2 tumor cells ( IRMBT-2) + IL-2 cells of CD4(+), CD8(+), CD44(+) and CD11b(+) phenotypes pr ominently infiltrate the subcutaneous local injection sites. In contrast, o nly scanty immune responding cells could be seen locally if treated with IR MBT-2 + IFN-a2b, albeit in the presence of interleukin-2 (IL-2). However, t he spleens of D17TBM treated with IRMBT-2 + IFN-a2b contained the highest p ercentage of CD44(+) memory T cells and cells of the CD11b(+) phenotype; mo reover, their natural killer (NK), lymphokine activated killer (LAK) and cy totoxic T lymphocytes (CTL) activities were significantly augmented. The re sults of in vivo tumor rechallenge revealed that administration of IFN-a, e ither alone or combined with IRMBT-2 could both effectively suppress the ou tgrowth of perioperative rechallenged tumor cells as well as prolong the su rvival of TBH. We conclude that despite the presence of autologous tumor va ccine, postoperative administration of IFN-a can further enhance the antitu mor immunity of TBH and therefore can be an effective adjuvant therapy to i mprove the therapeutic results of surgery on a tumor bearing host.