Curative intravenous adoptive immunotherapy of meth a murine sarcoma. A histologic and immunohistochemical assessment

Intravenous administration of 1.5 x 10⁸ syngeneic spleen cells from immune animals resulted in the complete eradication of established Meth A soft tissue sarcomas in (C57BL/6 x BALB/c) F₁ mice. In mice receiving a single injection of immune spleen cells 4 days after tumor implantation in the abdominal wall, the tumors continued to grow for approximately 1 week before undergoing regression. This delay before adoptive immunity is expressed is thought to represent the time needed for the passively transferred cells to give rise to a host response of sufficient magnitude to destroy the tumor. None of the mice receiving a similar number of control spleen cells were cured of their sarcomas. Successful therapy was dependent upon the transfer of viable, immune T lymphocytes and required prior irradiation of the tumor-bearing host in order to remove suppressor T cells. Utilizing sequential histologic and immunohistochemical techniques, we attempted to characterize the cellular events of tumor regression. The earliest histologic difference between animals treated with immune and nonimmune lymphocytes was in the number of lymphocytes detected at the perimeter of the tumor in specifically immunized mice on day 6. There was also a striking difference between animals treated with immune versus nonimmune lymphocytes in the intensity and timing of the acute inflammatory response beginning on day 8. The 'front' of immunologically mediated tumor destruction appeared at the lateral and deep borders of the implanted sarcomas and progressed inwards. During the period of active tumor regression T lymphocytes reactive with a biotinylated mouse anti-Thy 1.2 monoclonal antibody were increased in frozen sections of tumors in mice receiving immune cells relative to the controls. During the first 3 weeks following adoptive transfer of lymphocytes, T cells reactive with Lyt-1 biotinylated mouse monoclonal antibody (helper/inducer phenotype) outnumbered their Lyt-2 (supressor/cytotoxic) counterparts in frozen sections of tumor from both specifically immunized and control mice. By the end of the 4th week of the experiment, the sarcomas were completely eradicated in all mice receiving immune cells. The previous tumor beds were occupied by collections of lipid-laden macrophages, lymphocytes, plasma cells, and fibroblasts. Despite vigorous but delayed acute and chronic inflammatory responses at the tumor perimeters in the control mice, these tumors all progressed. Three to 4 weeks after tumor implantation, increased numbers of Lyt-2 lymphocytes were detected in frozen sections of tumors in the control mice, suggesting the possibility that Lyt-2 lymphocytes may function as suppressors of the host endogenous primary immune response against tumor.