MECHANISMS OF IMMUNE SUPPRESSION IN PATIENTS WITH HEAD AND NECK-CANCER - PRESENCE OF CD34(-MACROPHAGE COLONY-STIMULATING FACTOR() CELLS WHICH SUPPRESS IMMUNE FUNCTIONS WITHIN CANCERS THAT SECRETE GRANULOCYTE)

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF ) by murine tumors has been shown to induce immune suppressive cells h aving homology with GM progenitor cells, The purpose of this study was to determine if human head and neck cancers secrete GM-CSF, if this i s associated with an intratumoral presence of similar cells expressing the hematopoietic progenitor cell antigen CD34, and if such CD34(+) c ells suppress functions of intratumoral T cells, This was evaluated wi th fresh head and neck cancers, and in some instances regional lymph n odes and control tissue. Ten of the 14 squamous cell carcinomas (SCCs) studied secreted greater than 5 ng GM-CSF/g tissue, GM-CSP was not se creted in significant levels by either the other cancer types or by co ntrol normal muscle, Each of the high GM-CSF-secreting SCCs, but none of the cancers that did not secrete GM-CSF, contained cells expressing the hematopoietic progenitor cell antigen CD34 that had the capacity to grow into colonies in soft agar, Available regional lymph nodes fro m patients with high GM-CSF-pro ducing cancers also contained CD34(+) cells, Depletion of CD34(+) cells from dissociated cancers increased i nterleukin 2 secretion by the intratumoral lymphocytes while addition of the CD34(+) cells to dissociated cancers reduced interleukin 2 prod uction, indicating that the presence of CD34(+) cells within GM-CSF-pr oducing head and neck SCCs results in suppressed functional competence of lymphocytes within the SCCs. These results show that GM-CSF-secret ing SCCs contain cells expressing the hematopoietic antigen CD34 which are inhibitory to the capacity of lymphocytes within the SCCs to secr ete interleukin 2.