Depletion of T-cells with the CD4+CD45R+ phenotype in lymphocytes that infiltrate subcutaneous metastases of human melanoma.

We studied the phenotypes of lymphocytes extracted from 22 specimens of human melanoma, 11 s.c. metastases and 11 lymph node metastases, by two-color flow cytometry. Lymphocytes extracted from s.c. metastases were characterized by a significantly reduced ratio of CD4+ to CD8+ T-cells, as compared with peripheral blood lymphocytes from the same patients. Ten of 11 tumor-infiltrating lymphocytes from s.c. metastases, but only 1 of 11 peripheral blood lymphocytes, had a CD4/CD8 ratio of less than 1.0. This alteration was not observed for lymphocytes obtained from nodal metastases. Furthermore, almost all of the CD4+ T-cells in s.c. metastases expressed the antigen CD29w and were negative for the complementary antigen CD45R. In contrast, the CD29w/CD45R ratio of tumor-infiltrating lymphocytes from lymph node metastases was similar to that of matched peripheral blood lymphocytes. Thus tumor-infiltrating lymphocytes from s.c. metastases have the phenotype associated with true helper or antigen-committed T-cells, which could reflect their sensitization to tumor antigens, while tumor-infiltrating lymphocytes from lymph node metastases may represent merely an expanded residua of lymph node lymphocytes. Since tumor-infiltrating lymphocytes expanded in vitro are being tested as therapy for patients with advanced cancer, these observations may have important therapeutic implications.