Tumor-infiltrating T lymphocytes from renal-cell carcinoma express B7-1 (CD80): T-cell expansion by T-T cell co-stimulation.
B7-1 (CD80) provides co-stimulation for T-cell activation by interacting with CD28 or CTLA4. Here we demonstrate the expression of B7-1 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 B7-1 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 B7-1, and that mutual co-stimulation via the B7-1/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 B7-1 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.
Thurnher
M
M
Department of Urology, University of Innsbruck, Austria.
Radmayr
C
C
Hobisch
A
A
Böck
G
G
Romani
N
N
Bartsch
G
G
Klocker
H
H
D018122:B7-1 Antigen / Q000378:metabolism*; D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017493:Leukocyte Common Antigens