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Cellular changes and antitumor responses in the plasmacytoma-bearing mouse following cyclophosphamide treatment.

Abstract
Mice bearing the immunosuppressive plasmacytoma TEPC-183 exhibit a marked splenic hyperplasia. We have characterized these tumor-reactive splenocytes on the basis of cell surface marker expression, nonspecific 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. Fourteen days after tumor implantation, T-lymphocytes decreased from 70 million to 50 million per spleen. However, cells expressing Mac-1 antigen or nonspecific esterase activity increased from 10 to 65 million. This constituted a 6-fold increase in splenic macrophages. Further studies utilizing the expression of PC.2 antigen in conjunction with morphological examination indicated that metastatic TEPC-183 cells comprise approximately 5% of the tumor-host splenocyte population 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 antitumor response. Splenocytes, when assessed 1 wk following tumor ablation by cyclophosphamide, demonstrated antitumor 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 antitumor effect was glass nonadherent, nylon-wool nonadherent, 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.
AuthorsT C Shanahan, W S Ceglowski, H F Havas
JournalCancer research (Cancer Res) Vol. 45 Issue 12 Pt 1 Pg. 6463-70 (Dec 1985) ISSN: 0008-5472 [Print] United States
PMID2866030 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Surface
  • Receptors, Antigen, B-Cell
  • Thy-1 Antigens
  • Cyclophosphamide
  • Carboxylic Ester Hydrolases
  • Carboxylesterase
Topics
  • Animals
  • Antigens, Surface (analysis)
  • Carboxylesterase
  • Carboxylic Ester Hydrolases (metabolism)
  • Cyclophosphamide (therapeutic use)
  • Female
  • Immunity, Cellular
  • Immunosuppression Therapy
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis
  • Plasmacytoma (drug therapy, immunology, pathology)
  • Receptors, Antigen, B-Cell (analysis)
  • Spleen (enzymology, immunology)
  • Thy-1 Antigens

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