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-alpha (IFN-alpha) on the antitumor immunity of a tumor bearing host (TBH) when postoperatively administrated with or without lethally irradiated autologous tumor cells. Using the C3H/He-MBT-2 murine bladder tumor model, a status of postoperative residual tumor was mimicked by rechallenging tumor cells 24 hours after resecting the day-17 tumor. Using immunohistochemical analysis we demonstrated that after treating with lethally irradiated MBT-2 tumor cells (IRMBT-2) + IL-2 cells of CD4+, CD8+, CD44+ and CD11b+ phenotypes prominently infiltrate the subcutaneous local injection sites. In contrast, only scanty immune responding cells could be seen locally if treated with IRMBT-2 + IFN-alpha 2b, albeit in the presence of interleukin-2 (IL-2). However, the spleens of D17TBM treated with IRMBT-2 + IFN-alpha 2b contained the highest percentage of CD44+ memory T cells and cells of the CD11b+ phenotype; moreover, their natural killer (NK), lymphokine activated killer (LAK) and cytotoxic T lymphocytes (CTL) activities were significantly augmented. The results of in vivo tumor rechallenge revealed that administration of IFN-alpha, either alone or combined with IRMBT-2, could both effectively suppress the outgrowth of perioperative rechallenged tumor cells as well as prolong the survival of TBH. We conclude that despite the presence of autologous tumor vaccine, postoperative administration of IFN-alpha can further enhance the antitumor immunity of TBH and therefore can be an effective adjuvant therapy to improve the therapeutic results of surgery on a tumor bearing host.
Tzai
T S
TS
Department of Urology, Medical College, National Cheng Kung University, Tainan, Taiwan, Republic of China. tts777@ncku.edu.tw
Shiau
A L
AL
Wu
C L
CL
Chow
N H
NH
Tsai
Y S
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins