Tumor‐infiltrating T lymphocytes from renal‐cell carcinoma express B7‐1 (CD80): T‐Cell expansion by T‐T cell co‐stimulation

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Abstract
B7‐I (CD80) provides co‐stimulation for T‐cell activation by interacting with CD28 or CTLA4. Here we demonstrate the expression of B7‐I in freshly isolated and cultured lymphocytes from renal‐cell carcinoma. In fresh preparations of lymphocytes infiltrating renal‐cell‐carcinoma tissue, B7‐1 mRNA could readily be detected by reverse transcription PCR, and 2‐color flow‐ cytometry analysis revealed substantial B7‐1 expression on T cells from these isolates. As expected, tumor‐derived T cells also expressed CD28, the B7 receptor. While B7‐1 expression of tumor‐derived T cells was maintained during culture in interleukin‐2‐supplemented medium, CD28 expression was further enhanced. We also show that B7‐I is functionally involved in T‐cell expansion: anti‐B7‐1 MAb inhibited the PHA‐induced proliferation of tumor‐derived B7‐1+ T cells (35%) in the absence of exogenous antigen‐presenting cells, indicating that B7‐1 mediates T‐T cell co‐stimulation (self‐co‐stimulation). Our data demonstrate that T cells infiltrating renal‐cell carcinoma express B7‐I, and that mutual co‐stimulation via the B7‐I/ CD28 pathway contributes to the interleukin‐2‐driven expansion of tumor‐derived T cells in vitro. The frequency of B7‐1+ T cells in tumor lesions and the level of B7‐I on these cells may determine the time course of T‐cell expansion in vivo. Self‐co‐stimulation, however, might also represent one mechanism leading to the state of suppression or anergy characteristic of tumor‐infiltrating lymphocytes.