Clinical studies indicate a role of allogeneic hematopoietic cell transplantation (alloHCT) for patients with refractory or recurrent B-cell lymphoma (BCL) indicative of a graft-versus-tumor effect. However, the relevance of local immunosuppression in the BCL microenvironment by donor-derived regulatory T cells (Treg) after alloHCT is unclear. Therefore, we studied Treg recruitment after alloHCT in different murine BCL models and the impact of lymphoma-derived chemoattractive signals. Luciferase transgenic Tregs accumulated in murine BCL microenvironment and microarray-based analysis of BCL tissues revealed increased expression of CXCL9, CXCL10, and CXCL12. In vivo blocking identified the CXCR4/CXCL12 axis as being critical for Treg attraction toward BCL. In contrast to Tregs, effector T cells displayed low levels of CXCR4 and were not affected by the pharmacologic blockade. Most important, blocking CXCR4 not only reduced Treg migration toward tumor tissue but also enhanced antitumor responses after alloHCT. CXCL12 production was dependent on antigenpresenting cells (APC) located in the lymphoma microenvironment, and their diphtheria-toxin receptor (DTR)-based depletion in CD11c.DTR-Tg mice significantly reduced Treg accumulation within BCL tissue. CXCL12 was also detected in human diffuse, large BCL tissues indicative of its potential clinical relevance.In conclusion, we demonstrate that Tregs are recruited toward BCL after alloHCT by infiltrating host APCs in a CXCL12-dependent fashion. Blocking CXCR4 enhanced antitumor effects and prolonged survival of tumor-bearing mice by reducing local Treg accumulation, indicating that CXCR4 is a potential target to interfere with tumor escape after alloHCT.

Iron ore sintering is an important source of "dioxins", polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). This paper reports on attempts to identify materials, conditions, and mechanisms responsible for PCDD/F formation (i) by investigating salient properties of ores (viz., with respect to oxidation, condensation, and chlorination of model organics) and (ii) by mimicking the industrial process on a microscale with real-life materials. Principles of Design of Experiments (DOE) are employed. The reactivities of iron ores differ greatly. Limonite/goethite "soft" ore is a very active oxidation catalyst (e.g., for benzene and phenol), a property that may be useful in cleaning up crude sintering process offgases, whereas hematite/magnetite "hard" ore is not. The latter, however strongly promotes condensation of phenol to dibenzofuran. A newly built lab-microscale sintering facility could satisfactorily imitate the large-scale process, in part or as a whole. Results obtained with realistic feed mixtures point at dioxin formation in the sinter bed at levels significant enough to explain a major part of the outputs observed in the real-life process. With approximately 8 ppm (wt) of chloride added as NaCl, the PCDD/F output doubled, but with the same proportion of chlorine administered as C2Cl4, the dioxin output was over 2 orders of magnitude larger. The use of process reverts, etc. containing chlorinated organics should therefore be avoided. PCDD/F congener patterns are also reported and compared with those observed in practice.