Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P 5 .34), respectively; the overall survival rate was 79% and 82% (P 5 .36), respectively; cumulative incidences of relapse were 15% and 15% (P 5 .98); and those of the nonrelapse-mortality were 13% and 8% (P 5 .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediateor high-risk AML patients in CR1 lacking an identical donor. This trial was registered at www.chictr.org as #ChiCTR-OCH-10000940. (Blood. 2015;125(25):3956-3962)

• Acute myeloid leukemia (AML) patients present an altered glucose metabolism signature.• A panel of 6 metabolite biomarkers involved in glucose metabolism are identified with prognostic value for cytogenetically normal AML.Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients, including those with normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study that identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of wellestablished markers. We further compared the gene expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and trichloracetic acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (Ara-C), whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML. (Blood. 2014;124(10):1645-1654

Interleukin (IL)-17A is expressed in the tumor microenvironment where it appears to contribute to tumor development, but its precise role in tumor immunity remains controversial. Here, we report mouse genetic evidence that IL-17A is critical for tumor growth. IL-17A-deficient mice exhibited reduced tumor growth, whereas systemic administration of recombinant mouse IL-17A promoted the growth of hepatocellular carcinoma. The tumor-promoting effect of IL-17A was mediated through suppression of antitumor responses, especially CD8 þ Tcell responses. Furthermore, we found that IL-17A was produced mainly by Vg4 gd T cells, insofar as depleting Vg4 gd T cells reduced tumor growth, whereas adoptive transfer of Vg4 gd T cells promoted tumor growth. Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the infiltration of myeloid-derived suppressor cells (MDSC) to tumor sites in a CXCL5/CXCR2-dependent manner. IL-17A also promoted the suppressive activity of MDSC to reinforce suppression of tumoral immunity. Moreover, we found that MDSC could induce IL-17A-producing gd T cells via production of IL-1b and IL-23. Conversely, IL-17A could also enhance production of IL-1b and IL-23 in MDSC as a positive feedback. Together, our results revealed a novel mechanism involving cross-talk among gd T cells, MDSCs, and tumor cells through IL-17A production. These findings offer new insights into how IL-17A influences tumor immunity, with potential implications for the development of tumor immunotherapy. Cancer Res; 74(7); 1969-82. Ó2014 AACR.

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