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.
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.
Wiers
K
K
Department of Research Services, Hines V.A. Hospital, IL 60141, USA.
Wright
M A
MA
Vellody
K
K
Young
M R
MR
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D002762:Cholecalciferol / Q000008:administration & dosage*; D007111:Immunity, Cellular / Q000187:drug effects; D007116:Immunization, Passive; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D018952:Antigens, CD34; D002762:Cholecalciferol; D007371:Interferon-gamma