Using this setting, we could see here that NK cells from responder patients seem to have a stronger capacity to kill DTIC- pretreated cancer cells than NK cells from patients with progressive disease. This is coherent with the published literature, as Anne Caignard’s group described how NK cell phenotypes and functions vary according to tumor stage and treatment. Indeed, they showed that NK cell receptor NKP46 expression by NK cells seems diminished in patient bearing metastatic melanoma, and that chemotherapy could increase expression of NKP46 by NK cells, but IFNc secretion and degranulation are decreased after chemotherapy in ex-vivo assays, due to up-regulation of inhibiting factor NKG2A. They also showed no variation of NKG2D expression by NK cells after chemotherapy or according to tumor stage. Our data support that alkylating chemotherapy such as DTIC is only effective in patients with functional NK cells and support that either some patients have intrinsic more proficient NK cells or that the tumor drives an immunosuppressive state, which blunts NK cell function. The second hypothesis is more probable because we described that pretreatment of melanoma cell line with DTIC enhanced the cytotoxicity of NK cells from healthy volunteers and that high Lomitapide Mesylate number of Treg before chemotherapy is associated with absence of response to DTIC. Taken together, our study underscores some immune properties of DTIC and gives some preliminary data to isolate predictive Pancuronium dibromide factors of response. We believe that the two most promising factors are the importance of na? ��ve CD4 T cell number and NK cell activity to predict response to chemotherapy. First, our results show that high Treg number and low number of na? ��ve CD4+ T cells are associated with disease progression after chemotherapy. These patients are presumably those with exhausted memory cells and may greatly benefit from immune-based treatments, such as anti-CTLA4 or anti-PD1 antibody, because these two treatments aim to reverse immune inhibition and exhaustion. Furthermore, patients having highly cytotoxic NK cells could be better candidates to DTIC-based treatment, as they may benefit the most from its immune effects, enhancing NK- and CD8+ T cell based cytotoxicity. Larger studies are warranted to validate these results. The misfolding and subsequent polymerization of members of the serpin superfamily leads to a variety of diseases collectively known as the Serpinopathies. The most common pathological variant, accounting for 95% of all clinical cases, is the Z variant in which Glu342, which is located at the junction between the top of s5A and the base of the reactive center loop, is replaced by a Lys. The presence of this mutation results in the removal of both a salt bridge 
to Lys290 and a hydrogen bond to Thr203. The loss of these interactions brings about misfolding and polymerization of the protein within the endoplasmic reticulum of hepatocytes resulting in a lack of secretion and is characterized by a reduction in plasma levels to 10�C15% of normal. The polymerized Z a1AT damages the hepatocytes and predisposes the carrier to liver disease. The decreased plasma levels give rise to severe early onset emphysema. The molecular basis of Z a1AT polymerization is not completely understood. The structure, stability and polymerization characteristics of native Z a1AT have been studied using a range of biochemical and biophysical techniques. These data reveal that Z a1AT, in contrast to wild type a1AT, polymerizes rapidly when incubated at physiological temperatures.