LAUSR

We have read with interest the recent publication “Thera‐ peutic reduction of cell‐mediated immunosuppression in mycosis fungoides and Sézary syndrome” by Geskin et al. [1] and would like to comment on it based on our experience in tissue samples [2]. In their experiments on peripheral blood, Geskin et al. [1] observed no significant changes in myeloid derived suppressor cell (MDSC) dis‐ tribution comparing healthy volunteers to mycosis fungoi‐ des/Sézary syndrome (MF/SS) patients at different stages. However, the absolute number of MDSC was lower in > IB stage MF patients than in normal controls (p < 0.05); in the same patients, production of reactive oxygen species (ROS) by MDSC reached the highest values (p < 0.01), suggest‐ ing an increase in MDSC suppressive action despite their decreased number. Moreover, Geskin et al. [1] analysed MDSCs before and after four injections of PEGylated (PEG)‐IFN α2b (PEGIntron) at 1.25 μg/kg (one injection per week) in the same cohort of patients. While the MDSC number remained unchanged, a decrease in both ROS and arginase levels was observed only in patients showing a clinical response to therapy. The authors hypothesised that the therapeutic action of PEGIntron may be partially due to the inhibition of MDSC suppressive function [1]. Recently, our group investigated changes in the microenvironment of 46 MF cases at different stages [2]. An increase in arginase‐ 1‐positive MDSC was observed comparing patch and plaque lesions with tumour lesions (p < 0.01); we hypothesised that microenvironmental changes might influence disease progression. Taken together, the two contributions seem to support a role for MDSC in MF patients. The decrease of MDSCs in the blood of MF > IB observed by Geskin et al. [1] may be due to an accumulation of immunosuppressive cells in MF lesions, as observed in our series [2]. Immature MDSC accumulation in patch or tumour lesions may cause an increase in immunosuppressive cytokine release, such as IL‐4, IL‐10, TGF‐β contributing to tumour immune escape [3], and eventually leading to higher ROS and arginase levels in blood samples. Owing to the absence of a decrease in such levels in patients refractory to PEGIntron, we can speculate as to whether ROS and arginase levels should be investigated before the beginning of, and possibly during, any kind of therapy. The work of Geskin et al. [1] stresses the concept that new therapeutic options for decreasing MDSC accumu‐ lation in lymphoma or melanoma bearing‐mice [4], as well as reprogramming MDSC [5] from an immunosuppressive to an anti‐tumour role might also be adopted in MF. The results of Geskin’s [1] study and our own [2] will encourage researchers to further explore the functional role and thera‐ peutic use of MDSC in MF/SS.