CELLULAR CHANGES AND ANTI-TUMOR RESPONSES IN THE PLASMACYTOMA-BEARING HOST (IMMUNOLOGY, CYCLOPHOSPHAMIDE)

Mice bearing the immunosuppressive plasmacytoma TEPC-183 exhibit a marked splenic hyperplasia. These tumor-reactive splenocytes have been characterized on the basis of cell surface marker expression, non-specific esterase activity, and morphology. Although splenocyte numbers increased progressively throughout tumor growth, B and T lymphocytes, as defined by surface-immunoglobulin and Thy-1 antigen expression respectively, did not increase significantly. However, cells expressing Mac-1 antigen or non-specific esterase activity increased from 10 to 65 million. This constituted a sixfold increase in splenic macrophages. Further studies utilizing the expression of PC.2 antigen in conjunction with morphologic examination indicated that metastatic TEPC-183 cells comprise approximately 5% of the tumor-host splenocytes 14 days after implantation. Ablation of plasmacytoma by cyclophosphamide inhibited the tumor-associated splenocytosis and led to an increase in splenic T cells (from 70 to 120 million). In addition, macrophage numbers returned to normal.;This study also assessed the ability of splenocytes from animals with either actively growing tumors or those from cyclophosphamide-treated tumor-bearing mice to mediate an anti-tumor response. Splenocytes, when assessed 1 week following tumor ablation by cyclophosphamide, demonstrated anti-tumor activity in Winn neutralization assays. This activity was not detectable in splenocytes from animals with progressively growing tumors. Additional studies revealed that the cell population involved in the anti-tumor effect was glass non-adherent, nylon-wool non-adherent, and expressed Thy-1 antigen. These observations were consistent with the expansion of the splenic T lymphocyte population following cyclophosphamide treatment. However, the immune response directed against primary TEPC-183 tumor cells was not inhibitory to metastatic tumor cells.