Future perspectives: should Th17 cells be considered as a possible therapeutic target in acute myeloid leukemia patients receiving allogeneic stem cell transplantation?

Th17 cells seem to promote proinflammatory effects, and their development seems to depend on intracellular signaling initiated by IL1β, supported by IL6 and IL23 and mediated by STAT3 and RORC2. Even though primary human AML cells may affect Th17 development through their constitutive cytokine release, the levels of circulating Th17 cells in older patients with untreated AML do not differ from healthy controls and show only minor variations during and following conventional intensive chemotherapy. IL17-A is the signature cytokine of Th17 cells, but in vitro studies have failed to demonstrate a direct antileukemic effect of IL17 on primary human AML cells for most patient samples. However, several observations suggest that Th17 cells mediate antileukemic effects through other mechanisms and are important in allogeneic stem cell transplantation. Firstly, genetic variants in IL23/Th17 pathway have a prognostic impact with regard to both development of GVHD and posttransplant infections. Secondly, circulating IL17-secreting cells are detected during early posttransplant pancytopenia, and their ability to release IL17 is associated with later GVHD. Thirdly, a high number of Th17 cells in allogeneic stem cell grafts are associated with later acute GVHD, levels of circulating Th17 cells are increased at the onset of acute GVHD, and these levels normalize during treatment. In the present article, we review previous studies of Th17 cells in AML and in the development of GVHD, possible therapeutic strategies and available therapeutic tools for targeting of Th17 cells.