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Tumor burden impairment of murine natural killer cell cytotoxicity
M Boom1, R E Pollock, R R Shenk
1Department of General Surgery, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston.
Abstract:
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.
Insights
Natural killer cell cytotoxicity (NKCC) decreases with tumor growth, impacting metastasis control. Early intervention in tumor progression may enhance immunotherapy effectiveness against solid tumors.
Area of Science:
- Immunology
- Cancer Biology
- Oncology
Background:
- Natural killer (NK) cells play a role in controlling circulating tumor emboli.
- Suppression of NK cell cytotoxicity (NKCC) during tumor progression is a concern for solid tumor treatment.
- The relationship between tumor growth, metastasis, and NKCC requires further investigation.
Purpose of the Study:
- To examine the interplay between tumor progression, metastasis development, and NKCC.
- To determine the timing of NKCC suppression relative to tumor burden and metastatic activity.
Main Methods:
- Mice were inoculated with Lewis lung carcinoma (3LL) cells.
- Tumor growth, splenomegaly, and NKCC were monitored over time.
- 125I-labeled 5-iodo-2'-deoxyuridine (125I-IUDR) was used to detect pulmonary metastatic activity.
Main Results:
- Progressive decrease in NKCC was observed starting around day 6 post-inoculation, coinciding with primary tumor development.
- Significant splenomegaly was noted by day 12.
- Increased lung 125I-IUDR uptake, indicating metastatic activity, was detected from day 6 onwards, concurrent with NKCC impairment.
Conclusions:
- Tumor emboli implantation may occur early in tumor progression, before significant suppression of immune mechanisms.
- NKCC impairment begins early in tumor progression, potentially facilitating metastasis.
- Antitumor immunotherapy strategies may be more effective when targeted to earlier stages of tumor burden.