Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells.
Members of the TNF superfamily, including Fas, Fas ligand, and CD40, have been shown to be expressed on tumor cells. In the studies described in this work, we report that another family member, the ligand for 4-1BB (CD137), is expressed on various human carcinoma cell lines, on cells of solid tumors derived from these cell lines, and cells obtained from human tumors. Expression of 4-1BB ligand (4-1BBL) mRNA was detected by both RT-PCR and Northern blot analysis, and expression of 4-1BBL protein was detected by Western blot analysis of whole cell lysates and by FACS analysis of tumor cells and cell lines. Incubation of tumor cells with a 4-1BB-Ig fusion protein led to the production of IL-8 by the cells, demonstrating that the 4-1BBL is functionally active and signals back into the tumor cells. Furthermore, 4-1BBL expressed on the carcinoma cells functioned as a costimulatory molecule for the production of cytokines (most notably IFN-gamma) in cocultures of T cells and tumor cells. These findings suggest that 4-1BBL expressed on carcinoma cells may significantly influence the outcome of a T cell-tumor cell interaction.
Salih
H R
HR
Department of Immunology, Inflammation, and Pulmonary, Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
Kosowski
S G
SG
Haluska
V F
VF
Starling
G C
GC
Loo
D T
DT
Lee
F
F
Aruffo
A A
AA
Trail
P A
PA
Kiener
P A
PA
D053330:4-1BB Ligand; D015703:Antigens, CD; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D053330:4-1BB Ligand; D015703:Antigens, CD; D016207:Cytokines; D008024:Ligands; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma