Impairment of monocyte functions in advanced head and neck cancer

Depression of cell-mediated immunity is well established in most malignancies and especially in head and neck cancers, and much information is available concerning the defect in helper T lymphocyte function. We now report on impairment of the monocyte-macrophage system. Compared with normal controls we found that patients displayed, on one hand, an increased number of peripheral blood monocytes and, on the other hand, a smaller percentage of HLA-DR+ monocytes. Such peripheral blood monocytes normally failed to secrete factors, including interleukin 1 (IL-1). In addition, we observed that the in vivo induced blastogenesis of peripheral blood lymphocytes from patients, which is spontaneously depressed, is partly restored by medium containing IL-1. We cannot exclude, however, that the observed monocyte dysfunction involves other cytokines. Whether such an immune deficiency is due to secondary malnutrition or to the malignancy (or both) remains unclear.     

Quackery in head and neck cancer

Most human beings will do almost anything to prolong their existence or to relieve the suffering of disease. Others will do anything to exploit these desires by selling what they claim to be pain killing remedies or life prolongation nostrums. We present three cases of head and neck cancer patients; two used complementary and alternative medicine (CAM) prior to presenting to our service and the third declined conventional treatment to seek CAM instead. We discuss here the diagnosis, the time delay between CAM and commencement of conventional treatment, and the outcome in each case. Our aim is to define Quacks and to heighten public awareness of the potential harm they can cause.     

Intratumoral genomic heterogeneity in advanced head and neck cancer detected by comparative genomic hybridization

Little is known about the extent of intratumoral genetic heterogeneity in head and neck squamous cell carcinoma (HNSCC). We therefore examined 79 stage III and IV primary HNSCCs (P) and matched lymph node metastases (M) for over- and underrepresentation of specific chromosome regions by comparative genomic hybridization (CGH). The overall ratio of gains and losses was higher in metastases than in primary tumors (4/1 vs. 2.5/1). Gains of 3q (78.1% P vs. 87.5% M) and 11q (78.1% P vs. 62.5% M) and deletions of 3p (43.8% P vs. 34.4% M) and 9p (31.3% P vs. 15.6% M) were most frequently detected. The highest rate of intratumoral discordance was observed for primary tumors and corresponding metastases (32.8%) compared with matched pairs of two metastases (26.5%) and of two anatomically distinct sides of one primary tumor (24.3%). Furthermore, the discordance rate was dependent on the primary tumor site (oral cavity 49.2%, oropharynx 31%, hypopharynx 30.3%, and larynx 27.3%). In some tumors, the extent of genomic discordance argues against a monoclonal origin. In conclusion, we found a high individual variation of intratumoral genomic heterogeneity depending on the localization and selection of matched pairs. These findings are of specific importance in view of establishing prognostic markers.     

Growth of human squamous head and neck cancer in vitro.

This study was undertaken to define the cloning efficiency of squamous head and neck (H/N) cancer in soft agar. Twenty squamous cell carcinomas of H/N origin were mechanically dissociated and cultured in the human tumor clonogenic assay ( HTSCA ). No growth was observed. Nine ascites specimens from separate patients with ovarian cancer were cultured during the same time period, and six grew, all with more than 30 colonies per plate. Thirty-one additional H/N specimens were enzymatically dissociated and cultured in the HTSCA . Again, no growth was observed. Sixteen of these enzymatically dissociated specimens were simultaneously cultured in identical media without agar. Five specimens grew. We conclude that squamous carcinoma of H/N requires anchorage and fibroblast support for successful growth in culture. Suspension in semisolid media is less effective than liquid tissue culture systems for in vitro growth of this tumor type.     

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

OBJECTIVE:

This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment.

METHODS:

Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guérin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured.

RESULTS:

For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guérin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures.

CONCLUSION:

Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferon-gamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period.     

Anergy testing in patients with head and neck cancer

Patients with head and neck cancer were found to be deficient in were not clear [correction] Possible explanations include a change in T-lymphocyte numbers, particularly the helper/suppressor T-cell ratio, with the cause of this change still unknown. Tumor immunosuppressing factors and cancer-induced immunosuppression are proposed to be such causes. The deficiency of T cells resulted in an impaired cell-mediated immune response (CMIR), which lowered the host resistance, such facilitating the tumor to spread. As the CMIR can be evaluated by delayed hypersensitivity skin testing (= anergy screen), the objective of this study was to compare the CMIR function of patients with head and neck cancer to a non-cancer control group using this anergy screen. The study group consisted of 20 patients (17 males, 3 females, age range 10-76 years) with head and neck cancer, which were anti-HIV negative and had not received any therapy yet. The control group consisted of another 20 persons (17 males, 3 females, age range 21-72 years) without any cancer and who were also anti-HIV negative. Exclusion criteria were (1) eczema or skin disease in the area to be tested, (2) having received oral prednisolone within the last week and (3) an anti-HIV positive immune status. The antigens used in this study consisted of PPD (5 IU), tetanus toxoid (TT) (0.8 LF/ml and 1.6 LF/ml, Candida albicans (20 PNU/ ml and 200 PNU/ml), mumps-measles-rubella (MMR) vaccine (1:10 v/v and 1:5 v/v). The test was done by intradermal injection of 0.1 ml of each antigen. The anergy screen was considered positive when the test resulted in an erythema or induration larger than 5 mm at 72 hours after the injection. Complete anergy was diagnosed when there was no skin reaction at all, partial anergy when only 1 antigen tested positive and no anergy when there were positive skin reactions to two or more antigens. In the study group, 9 (45%) patients were diagnosed with complete anergy, 11 (55%) with partial anergy and none with no anergy, while in the control group, none were complete anergic, 3 (15%) were partially anergic and 17 (85%) had no anergy. There was a statistically significant difference (p < 0.01) between these two groups. In conclusion, patients with head and neck cancer seemed to have an impaired CMIR, with at least the partial anergy being statistical significantly different compared to the non-cancer group.     

Retinoids as chemopreventive agents in head and neck cancer

The role of retinoids as chemopreventive agents in head and neck malignancies is briefly described. The hypotheses of mechanisms of cancer prevention are discussed. A strong case is made for extension of recent work in this field of preventive cancer chemotherapy.