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Suppression of the in Vitro Secondary Response to Syngeneic Tumor and of in Vitro Tumor Therapy with Immune Cells by Culture-Induced Suppressor Cells¹

From the Division of Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195

Abstract

Mice with advanced disseminated syngeneic tumor can be successfully treated with a combination of chemotherapy and adoptively transferred syngeneic immune cells. We have previously demonstrated that in vivo primed cells secondarily sensitized in vitro became more effective in tumor therapy, whereas primed cells cultured for 5 days without tumor stimulation became less effective than an equal number of uncultured fresh primed cells. Therefore, we examined stimulated and unstimulated cultures of tumor-primed cells for the presence of culture-induced suppressor cells, and determined whether in vivo tumor therapy with immune cells could be inhibited by concurrent inoculation of immune effector cells and cultured normal spleen cells, which contain culture-induced suppressor cells but are devoid of additional effector cells.

The in vitro primary allogeneic response was suppressed by cultured normal spleen cells, or tumor-primed spleen cells previously cultured for 5 days with or without tumor stimulation. In vitro secondary sensitization to syngeneic tumor was suppressed by normal or tumor-primed cells that had previously been cultured for 5 days without stimulation. The majority of this suppression was mediated by T cells in the cultured populations.

The efficacy of fresh tumor-primed cells, as well as primed cells secondarily sensitized in vitro, in adoptive chemoimmunotherapy of advanced tumor was diminished by concurrent inoculation of cultured normal cells. The cells mediating suppression of in vivo therapy required previous in vitro culture for induction, and were radiation sensitive.

Footnotes

¹ This work was supported by Grant CA 10777 from the National Cancer Institute, National Institutes of Health.

² Drs. Greenberg and Cheever are American Cancer Socieity Junior Faculty Fellows.

³ Dr. Fefer is an American Cancer Society Professor of Clinical Oncology.