Monocytes, Dendritic Cells, Macrophages, T cells and Head and Neck Cancer : the effect of a thymic hormone preparation in restoring defective immune functions
(Monocyten, dendritische cellen, macrofagen, T-cellen en het hoofd/hals carcinoom: het effect van een thymushormoonpreparaat op het herstel van gestoorde afweer)
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It is generally accepted that cell mediated immunity (CMI) has more importance in the control of cancer than the antibody-mediated immune response. The cell mediated immune response is the basis of the so-called natural host resistance to cancer, which is also referred to as "immunosurveillance". Although the concept of immunosurveillance has been much debated over the past decades, there is now no doubt that suppression of the immune function increases the incidence of a few types of cancer. Also, spontaneous regression has been observed for some tumors, including melanoma, renal cell carcinoma, and lymphoma, and evidence for a role of immunosurveilance is well supported in these tumors. The role of a cell mediated immunosurveilance in patients with a head and neck squamous cell carcinoma (HNSCC) is less clear. Immunosuppressed patients do not develop head and neck cancer more frequently and spontanous regression is at most anecdotal. Despite this, defects of the CMI in HNSCC patients have extensively been documented. One of the first tests to reflect the status of the CMI which was found abnormal in HNSCC patients, was delayed type hypersensitivity (dth) as measured by skin reactions to ONCB- dinitrochlorobenzene). Ninetyfive percent of the normal adult popUlation react with a dth reaction towards skin-applied ONCB, however such a positive reaction is often absent in HNSCC patients. These observations have not led to a present clinical use of ONCB skin testing, but over the past decades other, more specified defects of the CMI have become clear. These defects are predominantly caused, on one hand by outside factors, like smoking, alcohol and malnutrition, on the other hand are CMI defects caused by factors resulting from, or produced by the tumor itself. In an effort to restore the immune defects, and to neutralize at least some of these immunosuppressive factors, or simply to boost the immune system, various immunotherapies have been attempted in HNSCC patients. These efforts have at present not led to positive clinical results that justify the widespread use of these strategies. Furthermore, it is not at all clear if the incapacity of the immune system to deal with tumor growth is the direct result of these so-called "defects" in the function of its various components and cells, or that the cancers have yet other more important mechanisms to escape a presumed immunosurveillance. Given the more widespread application of CD markers to identify various leucocytes (table I); given the ongoing discovery of new cytokines and growth factors, their role in tumor growth (control) and their potential therapeutic qualities; given the rapid development of new laboratory techniques including tumor genetics, and the lack of progression in treatment outcomes of HNSCC patients over the past 3 decades, head and neck cancer immunology will continue to be an important field of research.
The work in this thesis was financially supported by the Saul A. Silverman Family
Foundation and Temmy Latner/Dynacare as a Canada International Scientific
Program in Otolaryngology and by Serono.
- dendritic cells
- neck cancer
- monocyte polarization
- cell carcinoma