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Depletion of T-Cells with the CD4+CD45R+ Phenotype in Lymphocytes That Infiltrate Subcutaneous Metastases of Human Melanoma¹

Division of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [M. J. M., D. B.], and the Instituto Nazionale per la Ricerca sul Cancro di Genova, Sezione di Roma, Viale Regina Elena 324, Rome, Italy [G. C.]

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.

¹ This work was supported by NIH Grant CA 39248 from the National Cancer Institute and by funds from the Nat Pincus Trust and the Rae S. Uber Trust.

² To whom requests for reprints should be addressed.

Received 6/ 6/89. Revised 8/23/89. Accepted 8/30/89.