We hypothesized that the gene expressions of PBMC involved in the immune response to Ruxolitinib 941678-49-5 advanced stage NSCLC would be markedly different from those in healthy subjects, and that additional differences would be seen between RWJ 64809 cancer patients with adenocarcinoma and squamous cell carcinoma or between stage IIIB and IV. Furthermore, we aimed to improve the understanding of the molecular mechanisms that regulate immunopotentiation induced by combination chemotherapy with CDDP and GEM, with the hope that novel genes may be found to be over- or under-expressed after treatment, thus offering new insights into improving the efficacy of chemotherapy. A number of studies have applied DNA microarray technology to investigate gene expressions in patients with NSCLC. In one of these studies, which focused on gene expressions in the blood leukocytes rather than tumor tissues, 29 genes were found to be altered in patients with early-stage NSCLC compared to those with non-malignant lung conditions. The extent to which the leukocyte genes play a role in advanced NSCLC, and the effects of histopathology and tumor stage on gene signatures are unclear. Therefore, we extended our investigation into advancedstage NSCLC by analyzing whole-genome gene expression profiles in PBMC from patients with newly-diagnosed advanced stage NSCLC and histopathology of either AC or SCC. Furthermore, to establish a direct link between gene expression and chemotherapy, post-treatment PBMC from 17 patients who received at least four courses of combination chemotherapy with CDDP and GEM were obtained, and the effects of chemotherapy on global gene expression profiles were evaluated using microarray analysis. Lung carcinogenesis is a complex process involving epithelial mesenchymal transition, which is an unregulated process in a host environment with deregulated inflammatory responses that impair both innate and adaptive immunity and permits cancer progression. Although numerous gene expression prognostic signatures have been identified for NSCLC by cDNA microarrays in the last few years, most of these studies have focused on early stage cancers or responses to surgical therapy, and used tumor samples obtained before surgery for comparisons. In the current study, we identified IL4 pathway-associated genes in immune cells that showed differential expressions between patients with advanced stage NSCLC and age-, sex-, and co-morbidity-matched healthy controls, some of which could be reverted or progressed after a median of four courses of combination chemotherapy with CDDP and GEM. Moreover, we identified and validated S100A15 to be a novel biomarker of tumor staging and a predictor of poor treatment response or long-term outcomes in advanced stage NSCLC. Several different immunosuppressive cells, including myeloid derived suppressor cells, tumor-associated macrophages, and T regulatory cells have shown increased populations in the cultured PBMC from cancer patients, implying an important mechanism of tumor immune evasion. In animal models, MDSC have been shown to impair tumor immunity by suppressing T cell activation and inducing TAM activation, thereby enhancing a tumor-promoting Th2 response. Chemotherapy treatment with doxorubicin plus cyclophosphamide in breast cancer patients has been shown to result in a decrease.