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Splenic natural cytotoxic activity is enhanced during growth of a murine fibrosarcoma
J P MacIntyre1, D W Hoskin, B L Pope
1Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Abstract:
We have shown previously that the natural killer (NK) cell activity of DBA/2J mice bearing M-1 fibrosarcomas is consistently depressed at the later stages of tumor growth. The apparent mechanisms of inhibition are suppressor cell activation and prostaglandin E (PGE) production by tumor and lymphoid cells. In contrast, we show here that the natural cytotoxic (NC) activity of cells from the spleen, blood, and lymph nodes of mice bearing M-1 tumors is enhanced when compared to that of age- and sex-matched control mice. This enhanced NC activity does not appear to be due to increased cytolytic activity of macrophages but, rather, to enhanced cytolytic activity of multiple populations of non-adherent cells including B and T cells. Correlated with this is the finding that the NC activity of normal spleen cells is not inhibited in vitro by either PGE1 or PGE2 at levels which are inhibitory to NK cells. NC activity, although independent of PGE, is in fact enhanced by PGE1 in a dose-related fashion. These data indicate that NK and NC cells are regulated differently by PGE and during tumor growth. Utilizing a Winn assay, we also demonstrate that a cloned cell line with NC activity is capable of slowing tumor growth in vivo and that this action is improved if mice are treated with indomethacin concomitantly.
Insights
Natural killer (NK) cell activity decreases during tumor growth, while natural cytotoxic (NC) cell activity increases. Unlike NK cells, NC cells are not inhibited by prostaglandin E (PGE) and can slow tumor growth.
Area of Science:
- Immunology
- Cancer Research
Background:
- Natural killer (NK) cell activity in DBA/2J mice with M-1 fibrosarcomas is suppressed during later tumor growth stages, attributed to suppressor cells and prostaglandin E (PGE).
- This study investigates the contrasting behavior of natural cytotoxic (NC) cell activity in the same tumor model.
Purpose of the Study:
- To characterize the activity of natural cytotoxic (NC) cells in mice bearing M-1 fibrosarcomas.
- To determine the differential regulation of NK and NC cells by prostaglandin E (PGE) and during tumor progression.
- To evaluate the in vivo efficacy of NC cells in controlling tumor growth.
Main Methods:
- Comparison of NC cell activity in spleen, blood, and lymph nodes of tumor-bearing mice versus control mice.
- In vitro assessment of NC cell response to prostaglandin E1 (PGE1) and E2 (PGE2).
- Winn assay to evaluate the anti-tumor effect of a cloned NC cell line in vivo, with and without indomethacin treatment.
Main Results:
- NC cell activity was enhanced in spleen, blood, and lymph nodes of M-1 tumor-bearing mice compared to controls.
- Enhanced NC activity was attributed to non-adherent cells, including B and T cells, not macrophages.
- NC cell activity was not inhibited by PGE1 or PGE2, and was enhanced by PGE1 in a dose-dependent manner, unlike NK cells.
- A cloned NC cell line demonstrated in vivo tumor growth inhibition, which was augmented by indomethacin treatment.
Conclusions:
- NK and NC cells are differentially regulated by PGE and during tumor growth.
- NC cells, particularly B and T cell populations, exhibit enhanced activity during M-1 fibrosarcoma progression.
- NC cells possess anti-tumor capabilities in vivo, suggesting therapeutic potential, especially when combined with agents that modulate the tumor microenvironment.