The ultrastructural cellular kinetics of an in vivo model of immunologic rejection was studied with the strain-specific TA3-St mammary adenocarcinoma in C57BL/6 mice. The peritoneal cavity of tumor-challenged mice had numerous neutrophils, a few lymphocytes, and normal macrophages at early times after challenge. Neutrophils formed contacts with viable tumor cells, remained viable, nonphagocytic, and did not extrude their cytoplasmic granules. Tumor cells so contacted showed morphologic evidence of cell injury followed by cell death. Later times after tumor challenge showed numerous activated macrophages rapidly phagocytosing tumor debris resulting in complete elimination of tumor at 24 hr. These macrophage aggregates had numerous elongated interdigitated villi and a prominent fibrin meshwork associated with their processes and cell surfaces.
The findings in this study demonstrate the morphologic participation of neutrophils in tumor rejection with the later participation of phagocytic, activated macrophages whose surfaces were covered with fibrin. The mechanism for attraction and binding of neutrophils to target tumor cells is not known. Possible similarities to the recently described role for neutrophils in antibody-dependent cellular cytotoxicity should be considered. The mechanism of tumor killing by neutrophils was not apparent by ultrastructural analysis since extrusion of cytoplasmic granules was not present. Release of potent cytotoxic materials from these cells by other anatomic routes is postulated. Activated macrophages participated primarily as scavengers of dead tumor. The significance of their surface-associated fibrin meshwork requires further study.
This work was supported by United States Public Health Service Grant CA-19141 and American Cancer Society Grant IM-44A.