Failure of tumor-reactive lymph node cells to kill tumor in the presence of immune-suppressive CD34+ cells can be overcome with vitamin D3 treatment to diminish CD34+ cell levels

Clin Exp Metastasis. 1998 Apr;16(3):275-82. doi: 10.1023/a:1006501110857.


Growth of Lewis lung carcinoma (LLC-LN7) tumors results in an increase in CD34+ granulocyte-macrophage progenitor cells having natural suppressor (NS) activity. These CD34+ NS cells were capable of inhibiting the cytotoxic activity of tumor-reactive lymph node cells. In vivo studies showed that adoptive treatment of LLC-LN7 tumor-bearing mice with tumor-reactive lymph node cells plus IL-2 failed to reduce the development of metastases. Studies were conducted to determine if diminishing the levels of CD34+ NS cells would allow for improved anti-tumor effectiveness of the adoptively transferred cells. The suppressive activity of CD34+ cells toward the cytolytic activity of tumor-reactive lymph node cells could be blocked by in vitro culture of CD34+ cells with the differentiation-inducing hormone 1alpha,25-dihydroxyvitamin D3. Similarly, treatment of LLC-LN7-bearing mice with vitamin D3 alone diminished the levels of CD34+ NS cells within regional lymph nodes, spleens and tumors. This treatment resulted in an increased immune reactivity to autologous tumor, as shown by the production of IFN-gamma by lymph node cells in response to the presence of LLC-LN7 cells. The extent of tumor metastasis in mice receiving vitamin D3 treatment was also reduced. When tumor-reactive lymph node cells were adoptively transferred into these LLC-LN7-bearing mice that were receiving vitamin D3 treatment, there resulted a pronounced synergistic reduction in tumor metastasis. The results of this study show that treatment of tumor bearers with vitamin D3 to eliminate CD34+ NS cells improves the anti-tumor effectiveness of adoptively transferred tumor-reactive lymph node cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD34 / analysis
  • Carcinoma, Lewis Lung / immunology*
  • Cholecalciferol / administration & dosage*
  • Immunity, Cellular / drug effects
  • Immunization, Passive
  • Immunotherapy / methods
  • Interferon-gamma / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens, CD34
  • Cholecalciferol
  • Interferon-gamma