In order to investigate changes in local immunological response in the process of cancer development and growth, in terms of qualitative and quantitative changes in immunologically competent cells assembled at local regions as well as qualitative changes in cell combination of regional lymph nodes, samples of removed cervical cancer were examined from the viewpoint of immunohistochemistry. Anti-lysozyme antibodies were used for detection of marcrophages, leu 1 antibodies for general T-cells, leu 2a antibodies for suppressor T-cells, leu 3a antibodies for helper T-cells and anti-TdT antibodies for immature lymphocytes. B-cells were differentiated by anti-Ig antibodies. In dysplasia of the uterine cervix, carcinoma in situ and early invasive cancer, there appeared macrophages, not observed below the normal epithelium, in the stroma just below the epithelium. Also in the regional lymph nodes of the patients with these diseases, macrophages increased. However, in highly invasive cancer, macrophages markedly decreased, both inthe local regions and the lymph nodes.
Lymphocytes gathering around the cancerous lesions were observed only in small numbers in carcinoma in situ. They consisted mainly of mature T-cells in early invasive cancer, with B-cells little observed. In highly invasive cancer, the number of B-cells increased and there were numerous cells which could not be recognized by antibodies (leu 1, leu 2a and leu 3a) for identifying membrane differentiating antigens of T-cells. Since most were TdT-positive cells, they seemed to be immature lymphocytes derived from the thymus. However, in lesions classified as early invasive cancer or less severe diseases, TdT-positive cells were not detected.
On the other hand, the regional lymph nodes presented changes in cell combination. At the stage of carcinoma in situ and early invasive cancer, TdT-positive immature lymphocytes began to join mature lymphocytes. In the lymph nodes of highly invasive cancer, suppressor T-cells were scattered only in small numbers and helper T-cells were rarely present. In spite of these mature T-cells, the number of immature T-cells increased. In the lymph nodes developing metastases, such as in the local regions, B-cells assembled markedly around the metastatic lesions and not only mature T-cells but also immature T-cells decreased.
Also examined were the response to Con A of lymphocytes isolated by the discontinuous BSA density gradient technique, maturation to T-cells in the presence of thymus humoral factor (THF), and localization of TdT.
As a result it was revealed that with the growth of cancer, more lymphocytes with THE increased Con A response were distributed in the low density layer. Most lymphocytes in that layer showed TdT localization in the cytoplasm, while lymphocytes in the high density layer tended to have TdT localized in the nucleus.
The above results reveal that immunologically competent cells coping with cancer change in association with the development and growth of cancer, the immature type replacing the mature type, especially in the T-cell system. These facts are therefore suggestive of the possibility that the cellular immunological mechanism in cancer hosts may allow activation of the immunosuppressive mechanism with cancer growth as well as bring about exhaustion of the immunological system.
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