Differential effects of different cytokines on the tumorigenicity and immunogenicity of murine tumors.
BACKGROUND
Granulocyte-macrophage colony stimulating factor (GM-CSF) or other cytokine gene transfer into tumor cells makes an effective tumor vaccine. However, this technique is time consuming and it is not possible for routine use in every patient.


METHODS
The present study was designed to combine use of the irradiated B-16 cell line, a C57BL6 mice melanoma cell line, and cytokine (GM-CSF, interleukin-4 [IL-4], IL-10, or IL-12) manipulation, to enhance effectiveness of the tumor vaccine in prevention or reduction of subcutaneous tumor formation or pulmonary metastases.


RESULTS
The results of in vitro studies show that the cytolytic activity of the splenocyte was highest when IL-2 or IL-4 was added to the culture medium. Immune splenocytes demonstrated the same level of cytolytic activity regardless of whether the mice were immunized once, twice or thrice. The proliferation assay was higher in immune splenocytes compared with normal splenocytes. The results of both the subcutaneous and pulmonary tumor growth models showed that immunization alone retarded tumor growth and prolonged survival, and this effect was essentially the same regardless of the frequency of immunization. However, the effect was much stronger when IL-4 was used during immunization in the subcutaneous tumor model, whereas IL-12 was the most optimal cytokine in the pulmonary metastases model.


CONCLUSIONS
Different cytokines have different effects on immunization in different animal models even with the same tumor and animal. Careful selection of the appropriate cytokine for tumor vaccine immunization must be considered when different patterns of tumor recurrence are noted in clinical practice.
Chen
Y M
YM
Chest Department, Taipei Veterans General Hospital, Taiwan, ROC.
Tsai
C M
CM
Perng
R P
RP
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000627:therapeutic use*; D005260:Female; D007114:Immunization; D008175:Lung Neoplasms / Q000378:metabolism; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D012878:Skin Neoplasms / Q000517:prevention & control
D019496:Cancer Vaccines; D016207:Cytokines