Autoantibodies targeting tumor-associated antigens in metastatic cancer:Sialylated IgGs as candidate anti-inflammatory antibodies.

摘要

In addition to the well-established effector functions of IgGs, including direct cytotoxicity and antibody-dependent cellular cytotoxicity, some populations ofIgGs may exert anti-inflammatory effects. Here, we describe a population ofantibodies that form in the natural course of metastatic cancer and containglycans that terminate with sialic acid. We demonstrate that both the titer ofthese antibodies and their level of sialylation are relatively stable throughout the progression of metastatic melanoma. The sialylation pattern of theseantibodies somehow correlates with their specificity for tumor-associatedantigens, as IgGs targeting several antigens associated with infectious agentsare relatively poor of sialic acid. We also show that some antibodies targetingthe melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209(DC-SIGN). We propose that these antibodies are candidate anti-inflammatoryantibodies. The presence of anti-inflammatory antibodies in cancer patients mayexplain, at least in part, why tumors persist and spread in the host despitestrong tumor-specific humoral responses. The elucidation of the cellular andmolecular pathways involved in the induction of anti-inflammatory antibodiesspecific for tumor-associated antigens and their function may yield importantinsights into how tumors evade immune detection and progress.