Histological analysis of IL-2 induced regression of murine solid SL2-tumors.
When DBA/2 mice are inoculated both intraperitoneally (i.p.) and subcutaneously (s.c.) with syngeneic SL2 lymphoma cells and treated i.p. on day 10-14 with 20,000 units IL-2/day, about 50% of the mice reject both the ascitic tumour and the s.c. tumour. During IL-2 therapy large areas of necrosis appear in the solid SL2 tumours between day 12 and 15. Immunohistochemical studies show that only a small number of infiltrating cells is present in the tumours. The percentage of macrophages (MHC-II+) in the tumours is about 1 and the percentage of T-lymphocytes (alpha beta-TCR+) about 0.5. No differences in the numbers of infiltrating cells are seen in untreated and IL-2 treated tumour bearing mice. The tumour surrounding infiltrate consists mainly of mononuclear cells: about 50% macrophages, 20% CD8+ cells, and 15% CD4+ cells. No tumour-infiltrating cells were found that express the IL-2 receptor. We conclude that direct cytotoxic activity of tumour infiltrating cells cannot account for the rapid occurrence of necrosis. When L3T4+ cells were eliminated by treating the mice with alpha-L3T4 monoclonal antibodies before tumor inoculation and treatment with rIL-2, tumor eradication did not occur. So, L3T4+ helper T-cells are essential for IL-2-mediated tumour regression. Exogenous rIL-2 is not directly responsible for the induced tumour regression. A significant stagnation of intratumoural bloodflow is observed after histological analysis; yet it still needs to be determined whether this is the primary cause or consequence of the observed necrosis.
Maas
R A
RA
University Hospital Utrecht, Department of Pathology, The Netherlands.
Dullens
H F
HF
Henk
D
D
Van Weering
J
J
De Mik
H J
HJ
Koten
J W
JW
Belger
R J
RJ
Den Otter
W
W
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000494:pharmacology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000502:physiology; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000502:physiology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins