Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.

Cancer stem cells (CSCs) represent a subset of tumor cells that are responsible for recurrence and metastasis of tumors. These cells are resistant to radiotherapy and chemotherapy. Immunotherapeutic strategies that target CSCs specifically have provided initial results; however, the mechanism of action of these strategies is unclear. The data were requested from The Cancer Genome Atlas and Genotype-Tissue Expression, followed with the survival analysis and weighted gene co-expression network analysis to detect survival and stemness related genes. Patients were divided into three groups based on their immune status by applying single sample GSEA (ssGSEA) with proven dependability by ESTIMATE analysis. The filtered key genes were analyzed using oncomine, GEPIA, HPA, qRT-PCR, and functional analysis. Patients in a group with a higher stemness and a lower immune infiltration showed a worse overall survival probability, stemness and immune infiltration characteristics of breast cancer progressed in a non-linear fashion. Thirteen key genes related to stemness and immunity were identified and the functional analysis indicated their crucial roles in cell proliferation and immune escape strategies. The qRT-PCR results showed that the expression of PIMREG and MTFR2 differed in different stages of patients. Our study revealed a promising potential for CSC-target immunotherapy in the early stage of cancer and a probable value for PIMREG and MTFR2 as biomarkers and targets for immunotherapy.

Background The role of dysfunction of MCPH1, a recently identified tumor suppressor gene, has not yet been established in lung cancer. In our previous study, it was reported that MCPH1 expression is downregulated in lung cancer tissues and that MCPH1 overexpression inhibits the proliferation of non-small-cell lung cancer cells. The results can be found in the APJC and Oncology Letters journals. Methods Kaplan-Meier survival analysis was conducted to explore the prognostic significance of MCPH1. Cell experiments were performed to investigate the effects of MCPH1 on the biologic behaviors of lung cancer cells. Results In the current study, microarray analysis of MCPH1 revealed that lung cancer patients with high MCPH1 expression had longer relapse-free survival. Overexpression of MCPH1 in A549 lung carcinoma cells successfully inhibited cell migration and invasion. Moreover, overexpression of MCPH1 inhibited migration and invasion by regulating the activities of several proteins that control the epithelial–mesenchymal transition, such as Slug, Snail, E-cadherin, Mdm2, and p53. Conclusion Our results indicate that downregulation of MCPH1 correlates with tumor progression in lung cancer, and hence MCPH1 may be an important tumor suppressor gene and a novel candidate therapeutic target in lung cancer.

C-C chemokine receptor type 4 has been reported to correlate with lung cancer. However, the role of CCR4 in human non-small cell lung cancer patients is not well defined. Here, we demonstrated that increased expression of CCR4 was associated with clinical stage and CCR4 was an independent risk factor for overall survival in NSCLC patients. Moreover, tumor-infiltrating Treg cells were higher expression than matched adjacent tissues in CCR4+ NSCLC. Higher expression of chemokine CCL17 and CCL22 could recruit Treg cells to tumor sites in NSCLC. Treg in TIL exhibit a higher level of suppressive activity on effector T cells than matched adjacent tissues in NSCLC patients. Significant NK cell reduction was observed in tumor regions compared to non-tumor regions. NK cells demonstrated that reduced the killing capacity against target cells and the expression of CD69 + in vitro. The addition of Treg cells from NSCLC patients efficiently inhibited the anti-tumor ability of autologous NK cells. Treatment with anti-TGF-β antibody restored the impaired cytotoxic activity of T cells and NK cells from tumor tissues. Our results indicate that TGF-β plays an important role in impaired Teff cells and NK cells. It will therefore be valuable to develop therapeutic strategies against CCR4 and TGF-β pathway for therapy of NSCLC.

A spontaneous reversion that restores Wiskott-Aldrich syndrome protein (WASP) expression was reported recently. However, the genetic mechanism underlying the reversion event was unclear. In the present study, a WAS patient with a nonsense mutation (155 C>T, R41X) was followed during a three-year period. No expression of WASP was detected in peripheral blood mononucleated cells (PBMCs) in 2009 and a small population of intracellular WASP positive lymphocytes was detected during the following three years. The increasing trend of the revertant genotype was significant. WASP-expressing cells were present mainly CD56+ NK cells and CD8+ T cells. Sorted WASP+ cells were analyzed, indicating that the population of CD3+ T cells increased from 36.81% to 99.8%. Although the revertant cells in vivo may have a growth advantage, the patient presented a persistent autoimmune disease, thrombocytopenia, and died from extensive pulmonary fibrosis. The results suggest that the clinical consequences of T-cell mosaicism in WAS remain difficult to predict and is not sufficient to fully normalize immune functions in patients with WAS.

Autoimmune disease (AD) is common in patients with Wiskott-Aldrich syndrome (WAS) and patients with WAS who has an AD usually constitute a high-risk group with poor outcome. However, knowledge of AD in WAS is limited in China. In this study, medical records of 53 patients with WAS at Children´s Hospital of Chongqing Medical University from April 2004 to January 2014 were evaluated retrospectively and 14 patients (26%) had at least one AD. Autoimmune hemolytic anemia (AIHA) was the most common and detected in 12 patients (23%), other complications included immune thrombocytopenia (n = 1), immune neutropenia (n = 1), autoimmune arthritis (n = 1), and renal injury (n = 1). No significant differences were found in the level of serum immunoglobulins and lymphocyte subsets between the AD group and non-AD group. Although eight patients with AD received hematopoietic stem cell transplantation (HSCT), three patients died of pulmonary infection after HSCT.