We have shown that leukemic T cells from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ALCL) patients aberrantly express IL-22R1, the private receptor for IL-22, on their surface. This causes these cells to resemble a Th17 inflammatory cell type. The expression of IL-22R1 leads to IL-22 production, which then feeds back in an autocrine manner. This signaling also stimulates IL-17 in these cells that results in damaging systemic inflammation, a common complication seen in ALK+ALCL patients. We have shown that IL-22 may be a potential prognostic marker as it is likely a survival factor for the leukemic cells. The objective of the current study is to identify the role of the IL-22/IL-22R1 signaling pathway in ALK+ALCL development and during treatment. Since forced expression of IL-22R1 is sufficient to skew T cells to a Th17 phenotype and induce neutrophilia in vivo, targeting IL-22 may reduce inflammatory disease in ALK+ALCL patients. As IL-22 has proliferative effects, we hypothesized that IL-22 contributes to persistence of ALK+ALCL. We show that neutralizing anti-IL-22 antibody has a cytotoxic effect against an ALK+ALCL cell line when combined with a monoclonal anti-CD30 antibody. If neutralization of IL-22 shows therapeutic promise in our ALK+ALCL model, it could have rapid translational turnover.
- Copyright © 2013 by The American Association of Immunologists, Inc.