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
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.