Modulation of Murine Natural Killer Cells by a Granulocytosis-inducing Tumor¹

The nonmetastatic neutrophilia-inducing murine mammary carcinoma CE1460 has been shown previously to have profound effects on hemopoiesis and lymphopoiesis. In this report we examined the effects of progressive growth of CE1460 on natural killer (NK) cell activity both in the bone marrow, the site of primary NK cell production, and in a peripheral site, the spleen. (BALB/c × CE)F₁ mice were injected subcutaneously with trypsinized cells from in vivo passaged CE1460 or from B66, a BALB/c mammary carcinoma that does not induce neutrophilia. 3 days posttumor implantation, NK activity in bone marrow cells or spleen cells was greatly enhanced compared to normal controls. In B66 tumor-bearing mice, NK activity returned to normal by Day 7 and remained there through Day 14. In contrast, however, NK activity in CE1460 tumor-bearing mice decreased to only 10–20% of normal by Day 14. Excision of the tumor on Day 14, when WBC counts were three times normal, was followed by a rapid return of the WBC count to the normal range. NK activity in bone marrow and in spleen cells recovered somewhat but was still significantly suppressed 7 days after tumor excision. Limiting dilution analysis revealed a 3–5-fold decrease in frequency of NK precursors in bone marrow cells of mice bearing CE1460 for 7 or 14 days. The dramatic changes in NK activity observed in these experiments may reflect perturbation in production as well as an initial activation and subsequent suppression of mature NK cells.