Tumor burden impairment of murine natural killer cell cytotoxicity.

Natural killer (NK) cells may be important in the control of circulating tumor emboli. Because of this, the suppression of natural killer cell cytotoxicity (NKCC) observed with progressive tumor burden is a concern relative to the treatment of solid tumors. Our study examines the interplay between tumor progression, elaboration of metastases, and NKCC. Mice inoculated with Lewis lung carcinoma (3LL) cells developed visible primary tumors by day 6 of tumor bearing. This tumor burden appeared to be associated with a progressive decrease in NKCC beginning after day 6 of tumor bearing. Significant splenomegaly was observed beginning by day 12. Rapidly reproducing tumor cells take up 125I-labeled 5-iodo-2'-deoxyuridine (125I-IUDR) in lieu of thymidine more readily than normal cells. Intraperitoneal injection of the labeled IUDR allowed the identification of possible pulmonary metastatic activity earlier in the tumor progression sequence than has previously been possible using standard staining procedures. A significantly increased level of lung 125I-IUDR uptake was observed in the lung beginning after day 6 of tumor bearing; this increase in 125I-IUDR uptake began at the same time as the tumor burden impairment of NKCC. Successful implantation of tumor emboli may occur very early in experimental tumor burden systems, when measurable antitumor immune effector mechanisms are not yet massively suppressed. Antitumor immunotherapy programs may therefore need to be targeted to these earlier points of tumor bearing.