Helper T Cells Infiltrating Human Renal Cell Carcinomas Have the Phenotype of Activated Memory-Like T Lymphocytes

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Abstract
Human renal cell carcinomas are characterized by an inflammatory infiltrate containing many T lymphocytes. Attempts to grow T cells from such tumors by culture in interleukin (IL)-2 have yielded heterogeneous populations of cells with functional characteristics typical of lymphokine-activated killer cells obtained by similar culture of cells from peripheral blood mononuclear cells. We examined a panel of surface markers expressed on T lymphocytes to determine if the CD4+ T cells infiltrating human renal cell carcinomas are different from those in peripheral blood mononuclear cells. By flow cytometry analysis the CD4+ T cells in a panel of freshly digested human renal cell carcinoma primary and metastatic tumors expressed the activation markers CD69 and HLA-DR and manifested an increase in CD45RO and a reciprocal decrease in CD45RA expression as compared with peripheral blood CD4+ T cells. This suggests that CD4+ T cells infiltrating renal cell carcinomas are activated and have encountered antigen. However, the expression of the IL-2R alpha chain (CD25) was not different in tumor-infiltrating CD4+ T cells and peripheral blood CD4+ T cells, suggesting that T cells infiltrating human renal cell carcinomas may have a block in proliferative capacity. The general failure of cultured tumor-infiltrating lymphocyte (TIL) from renal cell carcinoma to demonstrate tumor-specific reactivity may be due to the failure of such cells to grow in IL-2.

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