HISTOLOGICAL ANALYSIS OF IL-2 INDUCED REGRESSION OF MURINE SOLID SL2-TUMORS

When DBA/2 mice are inoculated both intraperitoneally (i.p.) and subcu taneously (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 bo th the ascitic tumour and the s.c. tumour. During IL-2 therapy large a reas of necrosis appear in the solid SL2 tumours between day 12 and 15 . Immunohistochemical studies show that only a small number of infiltr ating cells is present in the tumours. The percentage of macrophages ( MHC-II+) in the tumours is about 1 and the percentage of T-lymphocytes (alphabeta-TCR+) about 0.5. No differences in the numbers of infiltra ting cells are seen in untreated and IL-2 treated tumour bearing mice. The tumour surrounding infiltrate consists mainly of mononuclear cell s: about 50% macrophages, 20% CD8+ cells, and 15% CD4+ cells. No tumou r-infiltrating cells were found that express the IL-2 receptor. We con clude that direct cytotoxic activity of tumour infiltrating cells cann ot account for the rapid occurrence of necrosis. When L3T4+ cells were eliminated by treating the mice with a-L3T4 monoclonal antibodies bef ore tumor inoculation and treatment with rIL-2, tumor eradication did not occur. So, L3T4+ helper T-cells are essential for IL-2-mediated tu mour regression. Exogenous rIL-2 is not directly responsible for the i nduced tumour regression. A significant stagnation of intratumoural bl oodflow is observed after histological analysis; yet it still needs to be determined whether this is the primary cause or consequence of the observed necrosis.