FAILURE OF TUMOR-REACTIVE LYMPH-NODE CELLS TO KILL TUMOR IN THE PRESENCE OF IMMUNE-SUPPRESSIVE CD34(-D-3 TREATMENT TO DIMINISH CD34(+) CELLLEVELS() CELLS CAN BE OVERCOME WITH VITAMIN)

Growth of Lewis lung carcinoma (LLC-LN7) tumors results in an increase in CD34(+) granulocyte-macrophage progenitor cells having natural sup pressor (NS) activity. These CD34(+) NS cells were capable of inhibiti ng the cytotoxic activity of tumor-reactive lymph node cells, In vivo studies showed that adoptive treatment of LLC-LN7 tumor-bearing mice w ith tumor-reactive lymph node cells plus IL-2 failed to reduce the dev elopment of metastases, Studies were conducted to determine if diminis hing the levels of CD34(+) NS cells would allow for improved anti-tumo r effectiveness of the adoptively transferred cells. The suppressive a ctivity of CD34(+) cells toward the cytolytic activity of tumor-reacti ve lymph node cells could be blocked by in vitro culture of CD34(+) ce lls with the differentiation-inducing hormone 1 alpha,25-dihydroxyvita min 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 tumors. This treatment resulted in an increased im mune reactivity to autologous tumor, as shown by the production of IFN -gamma by lymph node cells in response to the presence of LLC-LN7 cell s. The extent of tumor metastasis in mice receiving vitamin D-3 treatm ent was also reduced. When tumor-reactive lymph node cells were adopti vely transferred into these LLC-LN7-bearing mice that were receiving v itamin D-3 treatment, there resulted a pronounced synergistic reductio n in tumor metastasis, The results of this study show that treatment o f tumor bearers with vitamin D-3 to eliminate CD34(+) NS cells improve s the anti-tumor effectiveness of adoptively transferred tumor-reactiv e lymph node cells. (C) 1998 Lippincott-Raven Publishers.