Ability of low-dose cyclophosphamide to overcome metastasis-induced immunosuppression

Todd M. Tuttle, Martin Fleming, Paul S. Hogg, Thomas H. Inge, Harry D. Bear

Research output: Contribution to journalArticle

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Abstract

Background: Lymphocytes obtained from tumor-draining lymph nodes (DLN) can have potent in vivo antitumor activity after in vitro activation with bryostatin 1 and ionomycin. However, the presence of visceral metastases in the donor can inhibit the effectiveness of such lymphocytes. In the present study, we tested the ability of low-dose cyclophosphamide to overcome metastasis-induced immunosuppression in a murine model. Methods: Mice were injected with MCA-105 sarcoma cells in the footpad alone or in the footpad and the tail vein to establish lung metastases. Cyclophosphamide was given i.p. 1 day before harvesting the draining popliteal lymph nodes. For all donor groups, DLN cells were activated with 5 n M bryostatin 1 and 1 μM ionomycin and cultured for 7 days in 20 U/ml IL-2. Activated DLN cells were then adoptively transferred to syngeneic mice with 3-day lung metastases. Results: The adoptive transfer of DLN cells from mice with footpad tumors only significantly reduced the number of lung metastases compared to untreated mice. However, activated DLN cells obtained from mice with both footpad and lung tumors were significantly less effective. Treatment of similar donor mice with 10 mg/kg cyclophosphamide significantly improved the antitumor activity of adoptively transferred cells. This dose of cyclophosphamide did not reduce the number of cells obtained from each lymph node or the expansion of cell numbers in vitro. Conclusions: These results suggest that the administration of low-dose cyclophosphamide prior to harvesting DLN cells may improve the success of adoptive immunotherapy in cancer patients.

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalAnnals of Surgical Oncology
Volume1
Issue number1
DOIs
StatePublished - Jan 1 1994

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Cyclophosphamide
Immunosuppression
Lymph Nodes
Neoplasm Metastasis
Lung
Ionomycin
Tissue Donors
Neoplasms
Cell Count
Lymphocytes
Adoptive Immunotherapy
Adoptive Transfer
Sarcoma
Interleukin-2
Tail
Veins

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Ability of low-dose cyclophosphamide to overcome metastasis-induced immunosuppression. / Tuttle, Todd M.; Fleming, Martin; Hogg, Paul S.; Inge, Thomas H.; Bear, Harry D.

In: Annals of Surgical Oncology, Vol. 1, No. 1, 01.01.1994, p. 53-58.

Research output: Contribution to journalArticle

Tuttle, Todd M. ; Fleming, Martin ; Hogg, Paul S. ; Inge, Thomas H. ; Bear, Harry D. / Ability of low-dose cyclophosphamide to overcome metastasis-induced immunosuppression. In: Annals of Surgical Oncology. 1994 ; Vol. 1, No. 1. pp. 53-58.
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