CYTOLYTIC AND CYTOSTATIC ANTI-TUMOR ACTIVITIES OF MACROPHAGES FROM MICE INJECTED WITH MURINE SARCOMA-VIRUS

We have characterized the cytolytic activity of adherent cells isolated from enzymatically disaggregated tumors or from the peritoneum of mice injected with murine sarcoma virus (MSV) using an 18‐h51 Cr release assay and compared it with the cytostatic activity present in the same effector population. Cytolytic activity of peritoneal exudate cells peaked 14 days after inoculation of MSV. Injection of thioglycolate increased ten‐fold the number of cells recovered from each animal and these cells exhibited the same level of cytotoxicity as did those obtained from uninduced animals. Fourteen days after MSV inoculation, cytolytic activity was also detected in the adherent cells isolated from the tumor and these cells had higher levels of reactivity than the peritoneal cells. Several lines of evidence indicated that the cytolytic effector cells were macrophages: the effector cells were adherent and phagocytic; were inactivated by silica and carrageenan, and removed by the carbonyl iron/magnet technique; and were not affected by treatment with anti‐Thy 1.2 plus complement. Furthermore, the effector cells were heterogeneous since, when they were separated by 1 g velocity sedimentation, there were several peaks of activity corresponding to macrophages with different sizes. Cytotoxicity was not specific since several antigenically unrelated target cells could be lysed. Cytostasis was measured by performing cell counts on the target cells as well as by the usual growth inhibition assay in which incorporation of [3H]thymidine is used as the indicator of proliferation. At low A:T ratios (10:1 to 1.25:1) there appeared to be no cytolytic activity since there was no significant decrease In the number of target cells at any time during the incubation. However, there was marked inhibition of growth as measured both by cell counts and by [3H]thymidine incorporation. The lytic effects were only detected at A:T ratios approximately ten times higher than those required for the inhibition of proliferation. Therefore, macrophages that can exert cytolytic and cytostatic anti‐tumor activity are present within MSV tumors which subsequently regress. This suggests a role for the macrophages in the anti‐tumor immune response that may be complementary to the well‐established specific cytolytic activity of immune T lymphocytes. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company