Classifying the Microenvironment of Mesothelioma

https://openworks.mdanderson.org/sumexp21/1204/thumbnail.jp

Clinical and Environment Factors Impacting Malignant Pleural Mesothelioma Prognosis

View full abstracthttps://openworks.mdanderson.org/leading-edge/1012/thumbnail.jp

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field

Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas

Shared Nearest Neighbors Approach and Interactive Browser for Network Analysis of a Comprehensive Non-Small-Cell Lung Cancer Data Set

View full abstracthttps://openworks.mdanderson.org/leading-edge/1000/thumbnail.jp