Morphological observations during developing concomitant immunity against a C3H/He mammary tumor.

During the developing phase of concomitant immunity against primary s.c. implants of the mammary carcinoma MC2, responder cells identified as Lyt 1 and Lyt 2 T-cell subsets and B-cells showed little tendency to infiltrate among the cells of the implants and did not appear to have any direct cytotoxic effect. Macrophages were also not cytotoxic at this time, but they were closely associated with the formation of a fibrous cellular capsule, always found around tumors in arrested growth or in regression. After a period of growth, about 20% of the MC2 implants regressed spontaneously. Surgical disruption of the capsules formed around 5-week-old primary tumor implants did lead to more frequent regressions, showing that a capsule that could destroy a tumor slowly also shielded the tumor against highly activated and effective systemic rejection mechanisms. In mice less than fully immunized with 3-week-old primary implants, the accumulation of responder cells at a second implant was rapid, and the development of a capsule was accelerated. Only the macrophages had developed a tendency to infiltrate among the tumor cells. Implants in partially immune mice had a lower mitotic index than did implants in normal mice. Of the second implants, 30% did not reach palpable size, and 42% regressed after a period of growth. Only after at least 5 weeks of immunization did a rapid destruction of second implants become evident. The tumor-destructive process was associated with infiltration by activated macrophages and was completed in 3 to 6 days.