Increase of tumour infiltrating lymphocytes in mice treated with antimetastatic doses of NAMI-A

NAMI-A is a novel antitumour agent, based on ruthenium, which has proved ef fectiveness against lung metastases of solid mouse tumours. The study focus es on the effects of NAMI-A on leukocyte infiltration into the primary tumo ur of MCa mammary carcinoma, implanted subcutaneously (s.c.) or intramuscul arly (i.m.) into CBA mice. NAMI-A, given with a cycle of daily treatments f or six consecutive days on advanced tumours at 35 mg/kg/day, markedly reduc es lung metastasis independently of the tumour type (Lewis lung carcinoma, MCa mammary carcinoma or TS/A adenocarcinoma) being treated and of the site of tumour, implantation (s.c. or i.m.). The analysis of leukocyte infiltra tion of the primary tumour, performed on a single cell suspension of cells isolated from a Ficoll gradient on which a raw suspension of primary tumour cells was layered, showed NAMI-A to significantly increase tumour infiltra ting lymphocytes. These lymphocytes are almost all CD3+ cells with a signif icant increase of the CD8+ over the CD4+ subpopulation that reduces the hel per/suppressor ratio fr om 2.8 to 2.1. These data indicated the absence of toxicity of NAMI-A for tumour infiltrating lymphocytes and suggested that t his compound might even synergize in combined treatments with cancer immuno therapy.