MECHANISMS OF IMMUNE SUPPRESSION IN PATIENTS WITH HEAD AND NECK-CANCER - INFLUENCE ON THE IMMUNE INFILTRATE OF THE CANCER

Citation
Mri. Young et al., MECHANISMS OF IMMUNE SUPPRESSION IN PATIENTS WITH HEAD AND NECK-CANCER - INFLUENCE ON THE IMMUNE INFILTRATE OF THE CANCER, International journal of cancer, 67(3), 1996, pp. 333-338
Citations number
48
Categorie Soggetti
Oncology
ISSN journal
00207136
Volume
67
Issue
3
Year of publication
1996
Pages
333 - 338
Database
ISI
SICI code
0020-7136(1996)67:3<333:MOISIP>2.0.ZU;2-9
Abstract
Freshly excised human head and neck cancers (219 primary cancers; 64 m etastatic lymph node cancers) were analyzed for the immune inhibitory mediators released from the cancer tissues and the immune infiltrate w ithin the tumor. Significant levels of the immune inhibitory mediators transforming growth factor-beta (TGF-beta), prostaglandin E(2) (PGE(2 )) and interleukin-10 (IL-10) were released from these cancers. Also r eleased was granulocyte-macrophage colony-stimulating factor (GM-CSF), whose secretion was associated with an intratumoral presence of CD34( +) cells. We have previously shown that CD34(+) cells within human hea d and neck cancers are immune inhibitory granulocyte-macrophage progen itor cells. The presence of TGF-beta, PGE(2) and IL-10 was associated with a reduced content of CD8(+) T-cells within the cancers. The CD4() cell content appeared to be less affected by these immune inhibitory mediators. Instead, parameters indicative of CD4(+) cell function (p5 5 IL-2 receptor expression, release of IL-2 and IFN-gamma) were dimini shed in cancers that released higher levels of TGF-beta, IL-10 and GM- CSF and had a higher CD34(+) cell content. Furthermore, metastatic can cers released higher levels of the soluble immune inhibitory mediators and lower levels of IFN-gamma and IL-2 than did primary cancers, alth ough CD34(+) cells were similarly present in both primary and metastat ic cancers. Our results show that human head and neck cancers have a m ultiplicity of non-mutually exclusive mechanisms of immune suppression that are most prominently associated with reduced CD8(+) cell influx and reduced influx and altered function of intratumoral CD4(+) cells. (C) 1996 Wiley-Liss, Inc.