Immunohistological analysis of anti-melanoma host responses

Various clinical and experimental observations point to the existence of an immunological host defense in cutaneous malignant melanoma. To identify the major effector mechanisms mediating the specific anti-tumor immune response, we examined 23 benign and neoplastic melanocytic lesions (3 nevi, 14 primary melanomas, and 3 cutaneous and 3 systemic metastases) by quantitative immunohistology, and correlated these results with the histopathological and clinical subtypes of malignant melanoma. Our analyses indicate that CD3+ T-cell receptor alpha/beta-expressing lymphocytes are the prevailing leukocyte subset in primary as well as secondary malignant melanoma. We further observed that in early lesions (< 0.75 mm) of superficial spreading melanoma the vast majority of tumor-infiltrating lymphocytes (TIL) belong to the CD4+ subset and frequently express CD45RA antigens. In more advanced tumors, the contribution of CD8+ TIL gradually increases, indicating that the quality of the anti-tumor immune response changes during the course of the disease. Finally, we found that a varying percentage of cutaneous TIL express the cutaneous leukocyte antigen which is defined by the monoclonal antibody HECA 452 and preferentially expressed by skin-seeking memory T cells. In contrast, extracutaneous melanoma metastases (liver, brain, ovary) were completely devoid of HECA 452-reactive lymphocytes. These findings suggest that lymphocytes infiltrating cutaneous melanomas belong to a memory/effector T-cell subset functionally associated with the skin.