Treatment with IL-2 and IL-12 inhibits tumour cell division in SL2 lymphoma.
We examined which mechanism plays a dominant role in the rejection of solid SL2 lymphoma treated with locally applied IL-2 and/or IL-12. This treatment resulted in about 80% cures. There was a moderate influx of leukocytes in the tissue surrounding tumours; yet these cells failed to invade the solid tumours. Potentially cytotoxic cells were not observed in close proximity to areas of tumour cell death, indicating that cell-mediated cytotoxicity is not an important mechanism of tumour rejection in this model. Similarly, inhibition of blood vessel growth and/or blood vessel injury could be ruled out as mechanisms, since tumour rejection was not accompanied by decreased angiogenesis or blood vessel injury. We did observe that many tumour cells die via apoptosis or necrosis and that tumour cell division in cytokine-treated mice is inhibited. In conclusion, IL-2/IL-12-mediated tumour rejection in solid SL2 lymphoma is mainly due to a shifted balance between tumour cell death and tumour growth caused by inhibition of proliferation, rather than to direct cell cytotoxicity or destruction of blood vessels.
Masztalerz
Agnieszka
A
Department of Biochemistry and Cell Biology, Utrecht University, Yalelaan 1, Utrecht, The Netherlands.
Van Luyn
Marja
M
Werner
Naomi
N
Molema
Grietje
G
Everse
Linda Ann
LA
Otter
Willem Den
WD
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007962:Leukocytes / Q000276:immunology; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008854:Microscopy, Electron; D009336:Necrosis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D007376:Interleukin-2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D018664:Interleukin-12