INCREASED RECURRENCE AND METASTASIS IN PATIENTS WHOSE PRIMARY HEAD AND NECK SQUAMOUS-CELL CARCINOMAS SECRETED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND CONTAINED CD34(+) NATURAL SUPPRESSOR CELLS

Human head and neck squamous cell carcinomas (HNSCC) that produce high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) h ave been shown to contain CD34(+) natural suppressor cells that inhibi t the activity of intratumoral T-cells. The present study evaluated wh ether GM-CSF production and the presence of CD34(+) cells within prima ry HNSCC would translate into increased recurrence, metastasis or canc er-related death during the 2 years following surgical excision. Fresh ly excised primary HNSCC of 20 patients that subsequently developed di sease, and of 17 patients that remained with no evidence of disease we re analyzed for production of GM-CSF and for CD34(+) cell content. The cancers of patients that subsequently developed recurrences or metast atic disease produced almost 4-fold the levels of GM-CSF and had appro ximately 2.5-fold the number of CD34(+) cells as did cancers of patien ts that remained disease-free. In a second method of analysis, the pro gnostic significance of high vs. low GM-CSF and CD34(+) cell values wa s evaluated. These analyses showed that patients whose cancers produce d high GM-CSF levels or had a high CD34(+) cell content had a dispropo rtionately high incidence of recurrence or metastatic disease (94% and 100%, respectively), while the majority of patients whose primary can cers produced low levels of GM-CSF or had a low CD34(+) cell content r emained disease-free (16% and 19%, respectively). Our results indicate that the presence of CD34(+) cells in GM-CSF-producing HNSCC is assoc iated with a poorer prognosis for the cancer patients and suggest the utility of these parameters as prognostic indicators of outcome, Mecha nistically, our results suggest that the presence of immune suppressiv e CD34(+) cells in GM-CSF-producing HNSCC leads to increased tumor rec urrence or metastasis. (C) 1997 Wiley-Liss, Inc,.