1 Anti-drug Antibodies In Patients With BCR/ABL-negative Myeloproliferative Neoplasms Treated With Recombinant Human Interferon-A 2 Overexpression Of Golgi Membrane Protein 1 Promotes Non-small-cell Carcinoma Aggressiveness

The objective of this study was to characterize the incidence and impact of immunogenicity to interferon-α(IFN-α-2a,IFN-α-2b,and Peg-IFN-α-2a)over a period of 12 months in patients with BCR/ABL-negative myeloproliferative neoplasms(MPNs).A total of 131 patients from an observational prospective cohort were selected.Antidrug antibodies,in serial serum samples obtained monthly after initiation of therapy,were measured by ELISA and WISH/VSV CPE assays.The association between antidrug antibodies and treatment response and adverse effects was evaluated.Among patients who completed 12 months of follow-up,binding antibodies(BAbs)were detected in 53%of those receiving IFN-α(69 of 131)and neutralizing antibodies(NAbs)were detected in 19%(25 of 131).Nabspositivity was correlated with poorer clinical response,and Bab-positivity was associated with more adverse events.Almost all BAbs and NAbs appeared within 8 months after treatment began(95%).Complete remission(CR)rate was 62%for patients who were BAbs-positive and 69%for patients who were Babs-negative;however,the CR rate of patients with NAbs(+)(24%)was obviously lower than in patients with NAbs(-)(75%).Patients with BAbs(+)had more immune adverse effects(including fever,myalgia,skin reaction,and stomatitis)than BAbs(-)patients,and NAbs to IFN-α had no obvious influence on the adverse effects rate.Our results provided evidence that the development of BAbs and NAbs can adversely affect IFN-α treatment in patients with MPN.Non-small-cell carcinoma(NSCLC)is one of the most lethal malignancies of lung cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets.Recent reports show that Golgi membrane protein 1(GOLM1)is highly expressed in a variety of tumor cells,functions as a negative regulator of T cells and then promotes tumor progression.However,its expression and role in NSCLC remain unclear.Herein,we showed that GOLM1 was markedly up-regulated in NSCLC cell lines and clinical tissues.Clinically,NSCLC patients with high expression of GOLM1 had shorter overall survival(OS)and high GOLM1 expression in tumor samples was significantly related to malignant phenotype,such as lymph node metastasis and high tumor stage.Ectopic expression of GOLM1 in NSCLC cells induced epithelial-to-mesenchymal transition(EMT)and promoted proliferation,migration,and invasion of NSCLC cells in vitro.Furthermore,GOLM1 overexpressing significantly promoted the tumorigenicity of NSCLC cells in vivo whereas silencing endogenous GOLM1 caused an opposite outcome.Together,our results provided new evidence that GOLM1 overexpression promoted the progression of NSCLC and might represent a novel therapeutic target for its treatment.