Search

The chemotactic responsiveness of peripheral monocytes and the acid-phosphatase activity of tumor-infiltrating macrophages, as well as the ultrastructural appearance, were studied in 40 patients with squamous cell carcinoma of the head and neck. The chemotactic responsiveness was found to be decreased in carcinoma patients, and this value appeared to be positively correlated in individual patients with the number of tumor-infiltrating macrophages, as well as with the histologic grade of the tumor. Patients with poorly differentiated malignancies showed impaired monocyte chemotactic responsiveness and low numbers of tumor-infiltrating macrophages. Macrophages present in the parenchyma of the tumor showed a weak and diffuse pattern of acid phosphatase activity. The acid phosphatase activity of stromal macrophages was much stronger and distributed in foci. Electron microscopic examination of the parenchymal macrophages revealed low numbers of lysosomes and the presence of tumor cell debris in the cytoplasm of the cell, without any sign of a surrounding phagosomal membrane. Together with the weak cytochemical reactivity, this probably indicates the poor functional state of the phagocyte when infiltrated in the parenchyma of the tumor. Low molecular weight factors derived from the tumor are known to decrease chemotactic responsiveness of peripheral monocytes. The poor functional state of the macrophages infiltrated within tumor parenchyma might be explained by assuming that a high concentration of such factors in the near vicinity of malignant cells causes toxic effects in macrophages.

The cell surface expression of the thyroid microsomal antigen is confined to the apical microvilli of the polarized cells in intact or semi-intact thyroid acini. This makes it possible to envisage a pathogenetic role for the commonest antibodies found in thyroid autoimmunity by mechanisms involving complement- and antibody-dependent cytotoxicity. TSH rereceptor antibodies can now be differentiated into those that stimulate hormone synthesis and release (TSI), and those which mimic TSH in its growth-promoting function (TGI). TGI were demonstrated in goitrous Graves' disease and in some patients with euthyroid non-toxic goitres, diffuse or nodular, defining a new variety of thyroid autoimmunity. In patients with non-toxic goitre there is hardly any lymphoid thyroiditis and a low incidence of thyroglobulin or microsomal antibodies, the main expression of autoimmunity being the impetus to thyroid hyperplasia and hypertrophy. TSH receptor antibodies of both types, TSI and TGI, can either be stimulating or have blocking effects (TSI block and TGI block). Atrophy of the thyroid gland in myxoedema is due to blocking of the normal pituitary-controlled repair mechanism. In goitrous thyroiditis cell re-growth as a result of increased TSH can occur, as there are no blocking antibodies. In some patients with 'simple' euthyroid goitres, TSI blockers prevent the onset of hyperthyroidism while growth-promoting antibodies give rise to the goitre.

The accessory functions attributed to macrophages, such as antigen presentation, are probably carried out by specialized, marrow-derived cells which always have Ia antigen on their surfaces. These cells are not actively phagocytic, but are mainly engaged in engulfing large volumes on fluid. They are found in the epidermis as sessile cells, the Langerhans cells, but some re-enter the dermis and appear in afferent lymph as actively moving, veiled cells. Here they are joined by other veiled cells which have differentiated in the dermis: both populations then enter the draining lymph node. A similar process of differentiation probably occurs in other specialized tissues leading to the formation of cells that enter the afferent lymph and become veiled cells. In the lymph node, veiled cells localize in the paracortex or T-dependent area and later differentiate into another sessile cell type, the interdigitating cell. The life-style of this family of cells appears to be well-adapted for the transport of antigen into the paracortex, an area from which free antigen is largely excluded, and it seems likely that T-cell activation is triggered by the arrival of veiled cells bearing a new antigen on their surfaces.

Human leukocyte antigens (HLA) and immunoglobulin (Ig) allotypes were examined in 98 patients with single head and neck cancers, and in 51 patients with multiple primary tumors. Immunoglobulin allotype Km (1) was present in 4% of patients with multiple primary tumors versus 21% in patients with a single head and neck cancer. The frequency of HLA-B8, HLA-DR3, and HLA-DQW2 in patients with multiple primary tumors and of HLA-B8, and HLA-B45 in patients with a single head and neck cancer increased significantly as compared with the control population. Those data suggest genetic influences--next to environmental factors--on the pathogenesis of multiple primary tumors in head and neck squamous cancer. It might be worthwhile to use HLA typing and Ig allotyping in the selection of patients in whom aggressive screening for second tumors is mandatory.