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

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Abstract

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 1a,25-dihydroxyvitamin D 3. Similarly, treatment of LLC-LN7-bearing mice with vitamin D 3 alone diminished the levels of CD34 + NS cells within regional lymph nodes, spleens and tu mors. This treatment resulted in an increased immune reactivity to autologous tumor, as shown by the production of IFN-g by lymph node cells in response to the presence of LLC-LN7 cells. The extent of tumor metastasis in mice receiving vitamin D 3 treatment was also reduced. When tumor-reactive lymph node cells were adoptively transferred into these LLC-LN7-bearing mice that were receiving vitamin D 3 treatment, there resulted a pronounced synergistic reduction in tumor metastasis. The results of this study show that treatment of tumor bearers with vitamin D 3 to eliminate CD34 + NS cells improves the anti-tumor effectiveness of adoptively transferred tumor-reactive lymph node cells.

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