Patients with squamous cell carcinomas of the head and neck (HNSCC) have profound defects in their immune defenses. We have shown that among the mechanisms that contribute to this immune dysfunction are immune inhibitory CD34+ progenitor cells, whose levels become elevated in the peripheral blood and within the tumor tissue. One goal of our studies is to overcome the immune inhibitory activities of tumor-induced CD34+ progenitor cells by stimulating their differentiation into cells, such as dendritic or monocytic cells, that can stimulate immune reactivity to autologous cancer. Results of in vitro analyses with CD34+ suppressor cells of HNSCC patients and of in vivo studies in animal tumor models have shown the capacity of tumor-induced CD34+ cells to differentiate into cells that phenotypically resemble monocytic or dendritic cells. Whether these cells can differentiate into dendritic cells in HNSCC patients is currently being tested. Less clear is whether the pathway by which the tumor-induced CD34+ cells differentiate will result in cells having the full capacity to function as potent stimulators of immune reactivity to autologous tumor.