title: Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor.
abstract: Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine tumors has been shown to induce immune suppressive cells having homology with GM progenitor cells. The purpose of this study was to determine if human head and neck cancers secrete GM-CSF, if this is associated with an intratumoral presence of similar cells expressing the hematopoietic progenitor cell antigen CD34, and if such CD34(+) cells suppress functions of intratumoral T cells. This was evaluated with fresh head and neck cancers, and in some instances regional lymph nodes and control tissue. Ten of the 14 squamous cell carcinomas (SCCs) studied secreted greater than 5 ng GM-CSF/g tissue. GM-CSF was not secreted in significant levels by either the other cancer types or by control 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 from patients with high GM-CSF-producing cancers also contained CD34(+) cells. Depletion of CD34(+) cells from dissociated cancers increased interleukin 2 secretion by the intratumoral lymphocytes while addition of the CD34(+) cells to dissociated cancers reduced interleukin 2 production, indicating that the presence of CD34(+) cells within GM-CSF-producing head and neck SCCs results in suppressed functional competence of lymphocytes within the SCCs. These results show that GM-CSF-secreting SCCs contain cells expressing the hematopoietic antigen CD34 which are inhibitory to the capacity of lymphocytes within the SCCs to secrete interleukin 2.
authors.affiliation: Departments of Research Service and Otolaryngology, Hines VA Hospital, Hines, Illinois 60141, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Pak
authors.forename: M A
authors.initials: MA
authors.lastname: Wright
authors.forename: J P
authors.initials: JP
authors.lastname: Matthews
authors.forename: S L
authors.initials: SL
authors.lastname: Collins
authors.forename: G J
authors.initials: GJ
authors.lastname: Petruzzelli
authors.forename: M R
authors.initials: MR
authors.lastname: Young
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D016178:Granulocyte-Macrophage Colony-Stimulating Factor