Cytokines affect resistance of human renal tumour cells to complement-mediated injury.
Overexpression of membrane-bound complement regulatory proteins (mCRPs) on tumour cells may hamper the effect of immunotherapy with complement-activating monoclonal antibody (MoAb). Therefore, it is important to investigate whether cytokines can downregulate the expression of mCRP on tumour cells. In this study, the effect of 10 cytokines on the expression of the mCRP CD46, CD55 and CD59 and the renal tumour-associated antigen G250/MN/CAIX on four human renal tumour cell lines and proximal tubular epithelial cells was determined by flow cytometry. In addition, it was measured whether changes in the expression of the classical pathway regulatory proteins CD55 and CD59 had an effect on C3 deposition and lysis. Interleukin-1beta (IL-1beta) consistently downregulated the expression of CD46 and CD59; IL-4 consistently downregulated the expression of CD46 and transforming growth factor-beta1, consistently downregulated the expression of both CD46 and CD55. However, treatment with IL-1beta and IL-4 also decreased the expression of G250/MN/CAIX. Changes in the expression of CD55 and CD59 were associated with changes in the amount of C3 deposited and the extent of complement-mediated lysis, respectively. This suggests that clinical immunotherapy, consisting of treatment with cytokines and MoAb, may induce either up- or downregulation of CD55 or CD59 and thus affect the effectiveness of immunotherapy with MoAb.
Blok
V T
VT
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Gelderman
K A
KA
Tijsma
O H M
OH
Daha
M R
MR
Gorter
A
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D001483:Base Sequence; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007167:Immunotherapy; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003176:Complement C3; D016207:Cytokines; D007375:Interleukin-1; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D003165:Complement System Proteins; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases