Effects of splenectomy on the development of tumor-specific immunity.
We have previously reported on the antimetastatic effects of experimental adoptive immunotherapy using plastic adherent lymphokine-activated killer cells (A-LAK) cells (R. E. Schwarz et al. Cancer Res. 49: 1441, 1989). We have also reported that the spleen is a superior source of lymphocytes for A-LAK cell generation (R. E. Schwarz and J. C. Hiserodt, Med. Hypotheses 28: 165, 1989). This study, therefore, was designed to examine the effects of splenectomy itself on tumor growth in an experimental animal model. Natural killer (NK)-resistant MADB106 mammary adenocarcinoma cells were injected iv into F344 rats to generate multiple lung metastases. Splenectomies (Sx) were performed on Days -6, -3, -1, 0, 1, 3, 6, and 10, counted from the time of tumor injection. Groups consisted of six animals each, and sham-anesthetized and -operated animals served as controls. Splenectomies, if performed between Days -3 and +1, had significant antitumor effects as documented by the number of outgrowing surface metastases (5 +/- 7 vs greater than 300; P less than 0.0001) and by animal survival (greater than 100 vs 21 +/- 3 days; P less than 0.001). However, splenectomies, performed at an earlier or later stage, did not show these effects. Sx did not alter peripheral blood NK activity or the percentages of mononuclear cell subsets except for a slight decrease in the T-helper/T-suppressor ratio (P less than 0.04). Interleukin 2 (rhIL2), given at 2.5 X 10(5) U/kg/day for 3 days immediately after splenectomy, completely abrogated the observed antitumor effects. Subcutaneous tumor rechallenge of long-term surviving animals showed no tumor take in 87% of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwarz
R E
RE
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15260.
Hiserodt
J C
JC
D000818:Animals; D001696:Biomechanical Phenomena; D005434:Flow Cytometry; D007109:Immunity / Q000502:physiology*; D007111:Immunity, Cellular; D008297:Male; D009000:Monocytes / Q000502:physiology; D009374:Neoplasms, Experimental / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D013156:Splenectomy; D014407:Tumor Cells, Cultured / Q000637:transplantation