Human Cancer
Mechanisms of immune suppression in patients with head and neck cancer: Influence on the immune infiltrate of the cancer
M. Rita I. Young,
Mark A. Wright,
Yvonne Lozano,
John P. Matthews,
Janet Benefield,
M. Margaret Prechel,
Corresponding Author
M. Rita I. Young
Research Service, Hines VA Hospital, Hines, IL 60141
Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153
Research Service (151-Z2), Hines V.A. Hospital, Hines, IL 60141. Fax: (708) 216-2319Search for more papers by this authorMark A. Wright
Research Service, Hines VA Hospital, Hines, IL 60141
Search for more papers by this authorYvonne Lozano
Research Service, Hines VA Hospital, Hines, IL 60141
Search for more papers by this authorJohn P. Matthews
Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153
Search for more papers by this authorJanet Benefield
Research Service, Hines VA Hospital, Hines, IL 60141
Search for more papers by this authorM. Margaret Prechel
Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153
Search for more papers by this authorM. Rita I. Young,
Mark A. Wright,
Yvonne Lozano,
John P. Matthews,
Janet Benefield,
M. Margaret Prechel,
Corresponding Author
M. Rita I. Young
Research Service, Hines VA Hospital, Hines, IL 60141
Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153
Research Service (151-Z2), Hines V.A. Hospital, Hines, IL 60141. Fax: (708) 216-2319Search for more papers by this authorMark A. Wright
Research Service, Hines VA Hospital, Hines, IL 60141
Search for more papers by this authorYvonne Lozano
Research Service, Hines VA Hospital, Hines, IL 60141
Search for more papers by this authorJohn P. Matthews
Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153
Search for more papers by this authorJanet Benefield
Research Service, Hines VA Hospital, Hines, IL 60141
Search for more papers by this authorM. Margaret Prechel
Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153
Search for more papers by this authorFirst published: 29 July 1996
Citations: 124
Abstract
Freshly excised human head and neck cancers (219 primary cancers; 64 metastatic lymph node cancers) were analyzed for the immune inhibitory mediators released from the cancer tissues and the immune infiltrate within the tumor. Significant levels of the immune inhibitory mediators transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and interleukin-10 (IL-10) were released from these cancers. Also released 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 head and neck cancers are immune inhibitory granulocyte-macrophage progenitor cells. The presence of TGF-β, PGE2 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 (p55 IL-2 receptor expression, release of IL-2 and IFN-γ) were diminished in cancers that released higher levels of TGF-β, IL-10 and GM-CSF and had a higher CD34+ cell content. Furthermore, metastatic cancers released higher levels of the soluble immune inhibitory mediators and lower levels of IFN-γ and IL-2 than did primary cancers, although CD34+ cells were similarly present in both primary and metastatic cancers. Our results show that human head and neck cancers have a multiplicity 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. © 1996 Wiley-Liss, Inc.
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