Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes.
Tumors can escape immune recognition and destruction through the induction of apoptosis in lymphocytes. Although renal cell carcinoma (RCC) is able to prevent immune recognition, only a few genes (such as FasL) that are relevant for RCC immune escape have been identified so far. We have previously shown that some apoptosis-inducing genes are overexpressed in RCC. We hypothesized that these genes could be part of the immune-escape strategy of these tumors. Here we report that CD70, a cytokine overexpressed in RCC, promotes lymphocyte apoptosis through interaction with its receptor CD27 and with the intracellular receptor-binding protein SIVA. Apoptosis increased after cocultivating lymphocytes with the RCC cell lines A498 and CAKI2. The addition of recombinant soluble CD70 to both native lymphocytes and a T-cell cell line resulted in increased lymphocyte apoptosis as well. Furthermore, induced apoptosis could be partially blocked with anti-CD27 and anti-CD70 antibodies. Our results strongly indicate a role for CD70 and CD27 receptor in lymphocyte apoptosis within the tumor environment. Apoptosis mediated by exposure to the CD70 secreted by tumor cells may contribute to the failure of RCC patients to develop an effective lymphocyte-mediated antitumor response.
Diegmann
Julia
J
Core Unit Chip Application, Institute of Human Genetics and Anthropology, Friedrich Schiller University, Jena 07740, Germany.
Junker
Kerstin
K
Loncarevic
Ivan F
IF
Michel
Susanne
S
Schimmel
Bettina
B
von Eggeling
Ferdinand
F
D017209:Apoptosis; D053282:CD27 Ligand / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000276:immunology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007107:Immune System; D007680:Kidney Neoplasms / Q000097:blood* / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000737:chemistry; D008954:Models, Biological; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D053282:CD27 Ligand; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7